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Category Archives: South Dakota Stem Cells

Anika Therapeutics, Inc. (ANIK)’s Stock Is Buy After Today’s Significant Increase – The Lamp News

Posted: October 30, 2019 at 1:45 pm

Investors sentiment decreased to 1.4 in Q2 2019. Its down 0.37, from 1.77 in 2019Q1. It turned negative, as 16 investors sold Anika Therapeutics, Inc. shares while 42 reduced holdings. 35 funds opened positions while 46 raised stakes. 13.49 million shares or 3.81% more from 13.00 million shares in 2019Q1 were reported.Moreover, South Dakota Council has 0.05% invested in Anika Therapeutics, Inc. (NASDAQ:ANIK). 218,686 are held by Geode Cap Mgmt. Nelson Van Denburg And Campbell Wealth Group Ltd accumulated 13,306 shares or 0.1% of the stock. Oaktop Ii Lp owns 12,500 shares or 0.11% of their US portfolio. Thrivent For Lutherans holds 0% or 11,149 shares. 5,435 are owned by Jefferies Gru Limited Liability Corporation. Everence Cap Mngmt Incorporated accumulated 0.04% or 6,520 shares. Moreover, Deutsche Bank & Trust Ag has 0% invested in Anika Therapeutics, Inc. (NASDAQ:ANIK). Aqr Limited Com reported 6,013 shares stake. Glenmede Co Na holds 54 shares. The Illinois-based Nuveen Asset Mgmt Llc has invested 0% in Anika Therapeutics, Inc. (NASDAQ:ANIK). State Board Of Administration Of Florida Retirement owns 11,873 shares. Mark Sheptoff Finance Planning Ltd Limited Liability Company, a Connecticut-based fund reported 300 shares. Voloridge Invest Management Ltd holds 0.01% or 6,610 shares. Foundry Prtnrs Lc accumulated 0.09% or 54,915 shares.

The stock of Anika Therapeutics, Inc. (NASDAQ:ANIK) is a huge mover today! The stock increased 32.45% or $17.61 during the last trading session, reaching $71.88. About 498,503 shares traded or 144.39% up from the average. Anika Therapeutics, Inc. (NASDAQ:ANIK) has risen 39.72% since October 25, 2018 and is uptrending. It has outperformed by 39.72% the S&P500.The move comes after 6 months positive chart setup for the $990.72M company. It was reported on Oct, 25 by Barchart.com. We have $78.35 PT which if reached, will make NASDAQ:ANIK worth $89.16 million more.

More notable recent Anika Therapeutics, Inc. (NASDAQ:ANIK) news were published by: Benzinga.com which released: 42 Stocks Moving In Tuesdays Pre-Market Session Benzinga on July 30, 2019, also Seekingalpha.com with their article: Anika up 35% after Q2 beat Seeking Alpha published on July 25, 2019, Seekingalpha.com published: Pluristem Therapeutics and EDAP TMS among healthcare gainers; Align Technology among losers Seeking Alpha on July 25, 2019. More interesting news about Anika Therapeutics, Inc. (NASDAQ:ANIK) were released by: Benzinga.com and their article: The Daily Biotech Pulse: Setback For Bristol-Myers Squibb, Gemphire Explodes, Lillys Nasal Low Blood Sugar Drug Benzinga published on July 25, 2019 as well as Finance.Yahoo.coms news article titled: Heres What Anika Therapeutics, Inc.s (NASDAQ:ANIK) P/E Is Telling Us Yahoo Finance with publication date: August 23, 2019.

Anika Therapeutics, Inc., together with its subsidiaries, provides orthopedic medicines for patients with degenerative orthopedic diseases and traumatic conditions in the United States and internationally. The company has market cap of $990.72 million. The firm develops, makes, and commercializes therapeutic products based on its proprietary hyaluronic acid technology. It has a 35.24 P/E ratio. The Companys orthobiologics products comprise ORTHOVISC, ORTHOVISC mini, MONOVISC, and CINGAL for the treatment of osteoarthritis of the knee; HYALOFAST, a biodegradable support for human bone marrow mesenchymal stem cells used for cartilage regeneration and as an adjunct for microfracture surgery; HYALONECT, a woven gauze used as a bone graft wrap; HYALOSS used to mix blood/bone grafts to form a paste for bone regeneration; and HYALOGLIDE, an ACP gel used in tenolysis treatment.

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Anika Therapeutics, Inc. (ANIK)'s Stock Is Buy After Today's Significant Increase - The Lamp News

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Sanford stem cell trial crosses key threshold in offering …

Posted: March 8, 2019 at 6:42 am

Dec. 21, 2018

This paid piece is sponsored by South Dakota Biotech.

Sanford Research has hit a key milestone in its efforts to gain FDA approval for ground-breaking use of stem cells in orthopedics and is already pursuing new trials to broaden its efforts.

Early data has been released showing that the first patients who were part of a clinical trial using adipose-derived stem cells to treat rotator cuff tears had no harmful effects from the treatment.

We know all our patients were safe, but a significant amount of our patients also had pain relief and some function relief, said Tiffany Facile, Sanfords director of regenerative medicine.

That really contributes to the next phase.

The next step a phase two trial that is intended to show the treatments efficacy will include about 200 patients at 10 sites, starting in early 2019.

That study duration is about a year, Facile said.

Sanford has worked in partnership with a hospital in Munich, Germany, for years as the treatment was pioneered and offered to patients there. So while the results in the U.S. are welcomed, theyre not entirely surprising, she said.

We know from patients in Munich that there is relief. This is a confirmation of what we knew, but theres additional excitement because this could provide another treatment option for patients here, and it means a lot to me to be able to tell that to patients.

At the same time, Sanford is working through studies using adipose-derived stem cells to treat osteoarthritis in the wrist and in the back. Like the rotator cuff study, researchers have started by testing for safety and will follow with a trial for efficacy.

Sanford Health is well connected nationally and internationally in the regenerative medicine world, Facile said. I think because we have set the standard and maintained a great relationship with the FDA, we will continue to lead in this space.

Facile and David Pearce, executive vice president of innovation and research, will present in early 2019 at the World Stem Cell Summit in Miami, which features global leaders in the stem cell and regenerative medicine community.

Sanford is really trying to lead and be a good mentor for others to work with the FDA, Facile said. We can do it. We can do it the right way, but you just have to trust in the science and have science in the clinical application. We are sharing our story about how it can be done in the best way, and its an extreme honor.

Sanfords leadership in regenerative medicine is a huge asset in growing South Dakotas visibility within the bioscience industry, saidJoni Johnson, executive director of South Dakota Biotech.

This sort of activity in clinical trials is so exciting for our state, Johnson said. It broadens our relationships, leads to additional collaboration and helps continue to attract the sort of research talent that is lifting up our entire bioscience economy.

Sanfords success in pursuing stem cell clinical trials has bolstered its ability to recruit and collaborate, Facile agreed.

Its exciting. This is a competitive field, and were meeting with scientists nationally who are looking for clinical sites to conduct their studies, and Sanford is that place. Thats Sanford. So it gets me excited, and the fact that were following the FDA and bringing this treatment to patients in the right way is so important to take into consideration. Its the right thing for the patient.

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Stem Cells in Medicine | Rapid City, South Dakota 57701

Posted: February 10, 2019 at 3:43 pm

The most common and accepted use of stem cells in medicine is a bone marrow transplant in which physicians attempt to change a patients blood cells from one type to another. In the case of cancers like leukemia or diseases like sickle-cell anemia, the transplant aims to erase all the diseased cells and replace them with a new line of blood-type cells derived from donor stem cells. The process itself is painful and has variable success rates, but when it works patients can be cured.

The Fountain of Youth drove explorer Ponce de Leon to the discovery of new worlds, and this mythical fascination with renewal pre-dates the Ancient Greeks. Today, promise lies in small cells called stem cells that have the ability to self-renew and transform into cells of differing types. The International Society for Cellular Therapy has defined stem cells by the following criteria: (i) they are adherent to plastic material in the laboratory, (ii) they express specific proteins on their outer surface much like you have unique traits that identify your heritage, and (iii) these cells can be directed to transform into bone cells, fat cells, cartilage cells, etc. The potential to form new organs and to revitalize aged tissues are the reasons that stem cells are researched so intensely and need to be scrutinized carefully. Stem cells can be harvested from an embryo or an adult. Embryonic stem cells are removed in utero from a fertilized egg and these cells have the greatest potential; however, their acquisition is controversial and their use highly regulated. Adults have an abundant supply of stem cells originating from blood and tissues. Cord blood is a commonly harvested source of adult stem cells originating from the blood stream (hematopoietic stem cells).

In addition, stem cells are found in your fat, bones and cartilage to name a few sites. These cells are called mesenchymal stem cells and they differ from hematopoietic stem cells in the markers expressed on their surface. Differing stem cells appear primed to better renew differing tissues, and the key is determining the correct factors that drive these cells to become a certain tissue type. So far, there is much promise and a few successes utilizing stem cells to treat diseases. In addition to the bone marrow transplant, many clinical trials and experimental studies are underway attempting to harness the potential of stem cells. The few mentioned here are only the tip of a large and growing iceberg.

During a heart attack the muscle cells within the heart die and are replaced by scar tissue. Your heart then changes shape and size in an attempt to successfully pump blood again; however, it rarely recovers the same capacity it had before the attack. Current therapies aim to prevent a future attack; however, physicians in Europe are using stem cells retrieved from patients bone marrow to regenerate muscle in the scarred areas. The early results have shown a modest gain in muscle cells and function. Long-standing wounds from trauma, diabetes or venous insufficiency are a serious problem and can take up to years to heal, sometimes never closing at all. Recent studies using stem cells in fat taken from liposuction specimens have shown improved healing rates and new blood vessel formation in problem wounds. In our own lab at Emory University, we have shown a four-fold increase in blood vessel formation with the addition of these stem cells. The next step is to apply these techniques to improve the quality of damaged skin and organs.

The notions that paralyzed patients can walk again and that kidneys can be built in the lab are the reasons the U.S. government has invested heavily over the last decade in stem cell research. They are also the reasons that many companies and even physicians have licensed and marketed the promise of these cells without ensuring the efficacy. We have the basic building blocks, but directing these cells to become complete organs or prevent cancer is beyond our current knowledge. You should be excited at the future potential, but be cautious about current promises that appear too good to be true.

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Stem Cells in Medicine | Rapid City, South Dakota 57701

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75% of Cancer Stem Cells Died When Attacked By Compound in …

Posted: July 27, 2018 at 6:44 am

by Mary West

Potent cancer-fighters are hidden within the leaves, stalks, husks and stems of cruciferous vegetables like watercress and broccoli.

A study shows a compound and enzyme found in these foods can kill cancer stem cells, which is a discovery that could help prevent the re-occurrence and spread of some malignancies.

According to lead author Moul Dey, cancer stem cells present quite a danger. They are resistant to chemotherapy and radiation, so they continue to live in the body after such traditional treatments. While the stem cells only comprise about 5 percent of a cancerous tumor, they act like a ticking time bomb. These tiny cells are very difficult to detect in a tumor, she says. Its like finding a needle in a haystack. Consequently, they can migrate through the blood vessels, thus causing the cancer to metastasize.

When cruciferous vegetables are eaten, a compound and enzyme combine during the chewing process to form phenethyl isothiocyanate (PEITC). Scientists at South Dakota State University tested the effects of this substance, known as PEITC, on human cancer stem cells in a Petri dish. The results were impressive, as 75 percent of the cells died within 24 hours. Even low concentrations of it proved effective. This finding builds upon previous research that reveals the anti-cancer properties of similar foods.

When a tumor outgrows its blood supply, it sends a sign to surrounding tissues to deliver more nutrients and oxygen. Prior studies show PEITC switches off this sign.

Cruciferous vegetables include watercress, broccoli, cabbage, cauliflower, Brussels sprouts, radishes, arugula, bok choy, kale, turnips and rutabaga. The researchers found concentrations of PEITC were particularly present in land and watercress. If you want to ingest the amount of PEITC used in the research, eat a diet rich in these vegetables, especially watercress.

A study published in the American Journal of Clinical Nutrition found a daily serving of watercress can significantly curtail DNA damage to blood cells, a problem thought to be a major trigger of cancer. In addition, the vegetable boosted the ability of the cells to resist further harm perpetrated by free radicals. This study is one within a body of accumulating research that indicates watercress may reduce the risk of colon, breast and prostate cancer.

Live in the Now consulted Sylvia Melndez-Klinger, registered dietitian and leading expert in cross-cultural Hispanic cuisine as it relates to health. She shared the recipe below that combines two extraordinarily healthful foods: watercress and fatty fish. Everyone should aim to eat 2 to 3 servings of fish, especially those high in omega-3 fatty acids, each week to reap the benefits that include cognitive function, heart health and more, she says.

Tarragon Tuna Watercress Salad

1/2 cup reduced fat mayonnaise 1/4 cup low fat sour cream 1/4 cup fresh tarragon, chopped or 2 teaspoons dried 1 teaspoon grated lemon zest plus 1 tablespoon fresh lemon juice 2 5-ounce cans solid white albacore tuna fish in water, drained 2 green onions, sliced 2 celery stalks, sliced ground pepper to taste 1 pound watercress, thick stems removed

In a medium bowl, mix together the mayonnaise, sour cream, tarragon, lemon zest and juice. Gently fold in tuna fish, green onions, and celery. Season with pepper and serve over the watercress.Makes: 4 servings

Sources:https://www.yahoo.com/health/broccoli-watercress-may-hold-potent-118305401687.htmlhttp://news.therawfoodworld.com/how-to-kill-cancer-stem-cells/http://www.medicalnewstoday.com/articles/63314.phphttp://naturalsociety.com/watercress-block-breast-cancer-cell-growth/

Mary West is a natural health enthusiast, as she believes this area can profoundly enhance wellness. She is the creator of a natural healing website where she focuses on solutions to health problems that work without side effects. You can visit her site and learn more at http://www.alternativemedicinetruth.com. Ms. West is also the author of Fight Cancer Through Powerful Natural Strategies.

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75% of Cancer Stem Cells Died When Attacked By Compound in ...

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Current State Laws Against Human Embryo Research

Posted: June 22, 2018 at 12:48 am

Harmful experimentation on embryos is a felony in some states

Some members of Congress think that researchers should be able to obtain and destroy live human embryos for federally funded stem cell research. But such destruction of embryos for research seems to be illegal (regardless of its source of funding) in nine states. Therefore proposals for federal funding would force many taxpayers to approve destructive cell harvesting that is a felony in their home state.

Louisiana

Louisiana's law recognizes a human embryo outside the womb as a "juridical person," and prohibits the destruction of a viable fertilized ovum. La. Rev. Stat. tit. 9, 123, 129 (West 2000). It further states: "The use of a human ovum fertilized in vitro is solely for the support and contribution of the complete development of human in utero implantation. No in vitro fertilized human ovum will be farmed or cultured solely for research purposes or any other purposes." 122.

Maine

Maine's law prohibits the "use [of]...any live human fetus, whether intrauterine or extrauterine...for scientific experimentation or for any form of experimentation." Me. Rev. Stat. tit. 22 1593 (West 1992). A legal analysis commissioned by the National Bioethics Advisory Commission concluded that this law "ban[s] research on in vitro embryos altogether." NBAC, Ethical Issues in Human Stem Cell Research, vol. II, pages A-4, A-10.

Massachusetts

Massachusetts law prohibits "use [of] any live human fetus whether before or after expulsion from its mother's womb, for scientific, laboratory, research or other kind of experimentation." Mass. Gen. Laws ch. 112 12 J (a) I (West 1996). The section goes on to define "fetus" as including "an embryo." Ch. 112 12 (J) (a) IV.

Michigan

Michigan's law provides that "[a] person shall not use a live human embryo...for nontherapeutic research if...the research substantially jeopardizes the life or health of the embryo..." Mich. Comp. Laws 333.2685 (1) (West 1992). Performing such experimentation is a felony. 333.2691.

Minnesota

Minnesota's law prohibits using or permitting the use of "a living human conceptus for any type of scientific, laboratory research or other experimentation except to protect the life or health of the conceptus..." Min. Stat. 145.422 (West 1998). "Human conceptus" means "any human organism, conceived either in the human body or produced in an artificial environment other than the human body, from fertilization through the first 265 days thereafter." 145.421.

North Dakota

North Dakota law provides: "A person may not use any live human fetus, whether before or after expulsion from its mother's womb, for scientific, laboratory, research, or other kind of experimentation." N.D. Cent. Code 14-02.2-01(1) (Michie 1997). A legal analysis commissioned by the National Bioethics Advisory Commission concluded that this law "would ban embryo stem cell research using either IVF embryos or aborted conceptuses." NBAC, Ethical Issues in Human Stem Cell Research, vol. II, page A-4.

Pennsylvania

Pennsylvania's law prohibits "knowingly perform[ing] any type of nontherapeutic experimentation or nontherapeutic medical procedure... upon any unborn child..." Pa. Cons. Stat. tit 18. 3216 (a) (West 2000). Performing such experimentation is a felony. Id. "Unborn child" means "an individual organism of the species homo sapiens from fertilization until live birth." 3203.

Rhode Island

Rhode Island prohibits the use of "any live human fetus, whether before or after expulsion from its mother's womb, for scientific, laboratory research, or other kind of experimentation." R.I. Gen. Laws 11-54-1(a) (Michie 2000). A legal analysis commissioned by the National Bioethics Advisory Commission concluded that this law "ban[s] research on in vitro embryos altogether." NBAC, Ethical Issues in Human Stem Cell Research, vol. II, pages A-4, A-10.

South Dakota

Under a South Dakota law enacted in 2000, it is a crime to "conduct nontherapeutic research that destroys a human embryo," or to "conduct nontherapeutic research that subjects a human embryo to substantial risk of injury or death." S.D. Codified Laws 34-14-16, 34-14-17 (Michie Supp. 2001). It is also unlawful to "use for research purposes cells or tissues that [a] person knows were obtained" by doing such harm to embryos. 34-14-18. "Human embryo" means a living organism of the species Homo sapiens at the earliest stages of development (including the single-celled stage) that is not located in a woman's body." 34-14-20. Thus this law bans not only the destruction of the embryo to obtain stem cells (regardless of the source of funding), but also research using the resulting cells (regardless of whether the cells were harvested in that state or elsewhere).

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Blood and Marrow Transplant – avera.org

Posted: June 18, 2018 at 5:47 pm

When you or a loved one battle aplastic anemia, leukemia, lymphoma (Hodgkins and non-Hodgkins), multiple myeloma or myelodysplastic syndrome, rebuild your immune system with an infusion of healthy stem cells through a blood and marrow transplant (BMT) at the Avera Cancer Institute Sioux Falls in conjunction with the Avera Transplant Institute the regions only blood and marrow transplant program.

After high intensity chemotherapy or radiation therapy kills cancer cells, transplanting healthy blood and marrow cells helps fight disease.

Let Averas expert team offer guidance about the value of blood and marrow transplant for your specific situation. If youre eligible, theyll help you explore transplant options and identify the best ones for you. Approaches include:

The Avera Cancer Institute in conjunction with the Avera Transplant Institute is a designated Transplant Center by the National Marrow Donor Program. This means you gain access to a worldwide listing of potential blood and marrow donors, which may widen your options and speed your treatment.

Find the support you need through a BMT Connections support group. Whether youre a blood and marrow transplant patient or loved one, join us before, during and after the transplant procedure for discussion and encouragement.

Learn more about blood and marrow transplant services at Avera, including the latest news and patient and provider features in the Avera Transplant Institutes Blood and Marrow Transplant newsletter.

Help meet the need for healthy stem cells by becoming a blood and marrow donor. Avera McKennan Hospital & University Health Center is the only National Marrow Donor Program-approved apheresis stem cell collection center in South Dakota.

Each year, thousands of Americans are diagnosed with life-threatening diseases such as leukemia or lymphoma, for which a blood and marrow transplant may be the best and only hope for a cure. However, only 30 percent of people will find a suitable donor within their family. For the remaining 70 percent, an unrelated donor with a matching tissue type must be found.

To get started or find more information, visit Be The Match.

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Stem rust of wheat – American Phytopathological Society

Posted: November 23, 2016 at 3:47 am

Schumann, G.L. and K.J. Leonard. 2000. Stem rust of wheat (black rust). The Plant Health Instructor. DOI: 10.1094/PHI-I-2000-0721-01 Updated 2011.

DISEASE:Stem rust (black rust)

PATHOGEN:Puccinia graminis f. sp. tritici

HOSTS:Wheat and barley, common barberry (and some additional Berberis, Mahoberberis, and Mahonia spp.)

Authors Gail L. Schumann, University of Massachusetts, Amherst Kurt J. Leonard, U.S. Department of Agriculture, Agricultural Research Service, Cereal Disease Lab, St. Paul, MN

Stem rust was once the most feared disease of cereal crops. It is not as damaging now due to the development of resistant cultivars, but outbreaks may occur when new pathogen races arise against which the existing kinds of resistance are ineffective. Stem rust remains an important threat to wheat and barley and, thus, to the world food supply. Anton deBary first demonstrated the heteroecious life cycle of a rust fungus with Puccinia graminis, the causal agent of stem rust.

On wheat and other grass hosts: Plants do not usually show obvious disease symptoms until 7 to 15 days after infection when the oval pustules (uredinia) of powdery, brick-red urediniospores break through the epidermis (Figures 1, 2). Microscopically, these red spores are covered with fine spines (Figures 3, 4). The pustules may be abundant and produced on both leaf surfaces and stems of grass hosts. Later in the season, pustules (telia) of black teliospores begin to appear in infected grass species (Figure 5). Microscopically, teliospores are two celled and thick walled (Figure 6).

On barberry and other alternate hosts: Pycnia appear on barberry plants (Figure 7) in the spring, usually in the upper leaf surfaces. They are often in small clusters and exude pycniospores in a sticky honeydew (Figure 8). Five to 10 days later, cup-shaped structures filled with orange-yellow, powdery aeciospores break through the lower leaf surface (Figure 9). The aecial cups are yellow and sometimes elongate to extend up to 5 mm from the leaf surface (Figure 10). Microscopically, aeciospores have a slightly warty surface (Figure 11).

Rust fungi are obligate parasites. In nature, they require living host tissue for growth and reproduction; they cannot exist as saprophytes. In the absence of living host tissue, they survive as spores. In most rust fungi, only the teliospores are adapted to survive apart from a living host plant for more than a few months under field conditions.

Puccinia graminis is heteroecious. This word describes rust fungi that require two unrelated host plants, such as wheat and barberry, to complete their life cycle. Puccinia graminis is macrocyclic, producing all five spore stages: basidiospores, pycniospores (spermatia), aeciospores, urediniospores (uredospores), and teliospores. Anton deBary, in 1865, first recognized the nature of the heteroecious life cycle, but the role of each spore stage was not completely understood until John Craigie, a Canadian scientist, studied the pathogen in 1927.

Although stem rust is caused by a single species of fungus, Puccinia graminis, there is considerable genetic variation within the species. In 1884, Eriksson discovered host-specific subspecies or "special forms" of the fungus. Each special form is designated in Latin as a forma specialis or "f. sp." All of the formae speciales have an identical appearance, but vary in host range. The pathogen that causes stem rust of wheat (Triticum aestivum) is Puccinia graminis f. sp. tritici. Other formae speciales include P. graminis f.sp. secalis, causal agent of stem rust of rye (Secale cereale), and P. graminis f.sp. avenae, causal agent of stem rust of oat (Avena sativa). Both Puccinia graminis f. sp. tritici and P. graminis f.sp. secalis cause stem rust in barley. About 1916, E.C. Stakman and others determined that within P. graminis f.sp. tritici are further genetic subdivisions called races. Later, races were found within other formae speciales as well.

The disease cycle of wheat stem rust starts with the exposure of each new wheat crop to spores of Puccinia graminis f. sp. tritici, which are the primary inoculum. The source of the first spores that infect the new wheat crop differs depending on the region in which the wheat is grown. In warm climates, wheat is planted in late fall and harvested in early summer. The first spores to infect the young wheat plants in the fall are urediniospores. They generally come from infected volunteer wheat plants. Seed spilled in the field or on roadsides at harvest time often sprout and produce scattered volunteer plants. These plants can become infected from spores produced on late-maturing wheat plants still in the field. The infected volunteer wheat plants serve as a bridge that carries P. graminis f. sp. tritici through the summer to the next fall-sown crop of wheat.

In regions with temperate climates, wheat may be planted either in the fall (winter wheat) or the spring (spring wheat) depending on the severity of the winters (Figure 12). For example, few winter wheat varieties can survive well through the severe winters of Minnesota, North Dakota, and Manitoba, so most of the wheat grown there is spring wheat. The first rust spores to infect wheat in the spring in temperate regions may be aeciospores from barberry, the alternate host, or urediniospores from infected wheat in distant regions with milder winters. Therefore, we describe two disease cycles for stem rust - with or without barberry.

Disease cycle, with barberry Barberry is the most dangerous source of primary inoculum of stem rust in temperate regions. If barberry grows near wheat fields, it will be a consistent source of aeciospores for the earliest infections of wheat in the spring (Figure 13).

Puccinia graminis overwinters as black, thick-walled, diploid teliospores that are produced on wheat or other grass hosts toward the end of the growing season (Figure 5). Karyogamy (fusion of two haploid nuclei to form a diploid nucleus) and meiosis (reduction division to produce four haploid basidiospores) take place in the teliospore. Teliospores are produced in a telium.

In the spring, each teliospore germinates to produce thin-walled, colorless, haploid basidiospores (Figure 14). Basidiospores infect the alternate hosts such as common barberry.

Basidiospores germinate and produce a haploid mycelium which colonizes the leaf tissue. From this mycelium, pycnia are formed inside the leaf but with the tops extending through the surface, usually in the upper surface, of barberry leaves. Pycnia produce receptive hyphae and pycniospores (Figure 15). No further development will occur until the receptive hyphae in the pycnium are fertilized by pycniospores from a pycnium of a different mating type. Pycnia and pycniospores are referred to as spermagonia and spermatia by some authors, but the former are the preferred terms of rust specialists.

Pycniospores (Figure 16) are produced in a sticky honeydew that is attractive to insects and helps ensure that successful cross-fertilization occurs (figure 8). Insects carry pycniospores from one pycnium to another as they forage across the leaves feeding on the honeydew. Splashing raindrops also disperse pycniospores and aid in cross-fertilization. Fertilization of pycnia is critical in the rust fungus life cycle, because it gives rise to the dikaryotic mycelium. After the nucleus of the pycniospore joins that of the receptive hypha, the paired, haploid nuclei divide in tandem in the mycelium throughout the remaining stages of the life cycle. All stem rust infections of wheat or other grasses involve dikaryotic spores and dikaryotic mycelium.

Over a period of days, the dikaryotic mycelium grows through the barberry leaf until a new structure, the aecium, breaks through the lower surface of the leaf to release the dikaryotic aeciospores (Figure 10). Aeciospores, although produced on barberry plants, can infect only wheat or other grass host of P. graminis. Aeciospores (Figure 11) differ from urediniospores, which also infect wheat, in their appearance - slightly warty rather than spiny - and in the way in which they are formed - in chains in an aecium rather than on individual stalks in a uredinium.

On wheat, aeciospores germinate, the germ tubes penetrate into the plants, and the fungus grows as dikaryotic mycelium. Within 1 to 2 weeks, the mycelium in each infection produces a uredinium filled with brick-red, spiny, dikaryotic urediniospores that break through the leaf or stem epidermis (Figure 1).

In heteroecious rusts, this important spore stage is called the "repeating stage," because urediniospores are the only rust spores that can infect the host plant on which they are produced. Under favorable environmental conditions, multiple, repeated infections of the same wheat plant and neighboring wheat plants can result in explosive epidemics.

Toward the end of the growing season, black overwintering teliospores are formed in telia (Figure 5), and the life cycle is completed. Because karyogamy and meiosis take place in the teliospore (Figure 6), this spore stage is an important source of genetic recombination in addition to its role as a survival spore.

Disease cycle, without barberry In North America, stem rust epidemics can occur in temperate regions even if barberry is not present (Figure 17). In the absence of barberry, the first spores of P. graminis to reach wheat in the spring are windborne urediniospores produced on winter wheat crops to the south (Figure 18). The mild climate along the coast of the Gulf of Mexico allows P. graminis to survive and spread in fields of winter wheat. Prevailing southerly winds in the spring carry the urediniospores north into the central Great Plains where they infect other winter wheat plants. Weather in the central Great Plains is usually too cold to permit stem rust infections during the winter. When spring wheat begins to grow in the northern Great Plains, it may be infected by windborne urediniospores from either the central or southern Great Plains. The stem rust disease cycle in the North ends with the wheat harvest.

In the South, the stem rust disease cycle starts with urediniospores that infect winter wheat seedlings after the fall planting. Most, if not all, of the primary inoculum is local. It comes from volunteer wheat plants that sprouted and became infected in the summer. Spread of urediniospores from north to south is not likely to be important. Spring wheat in the North is harvested in August, long before the new winter wheat crop has emerged in the South, where planting may not start until October or later. Barberry plants do not become infected in the South, so they are not a factor in stem rust epidemics there. This is because P. graminis teliospores will not germinate unless exposed to extended periods of freezing temperatures.

Stem rust is favored by hot days (25-30C/ 77-86F), mild nights (15-20C/ 59-68F), and wet leaves from rain or dew. Both aeciospores and urediniospores require free water for germination as do the other spore stages. Infections occur through stomata.

The source of inoculum can be predicted from the pattern of the rust disease. If inoculum comes from barberry, a point source, the resulting disease pattern is usually fan-shaped with the alternate host at the apex of the fan (Figure 13). If disease has a more uniform pattern, the inoculum source is usually from a broad area, such as the southern wheat crops (in the northern hemisphere) from which urediniospores are released. Scattered infections mainly on the top leaves in a wheat field indicate that airborne spores were carried into the field from an external source. Rainfall is important for spore deposition during long distance dispersal of the spores.

If disease develops in individual foci within a wheat field, the source of urediniospores is probably overwintering mycelia and/or uredinia. Rusted plants in foci from overwintering sources have heavy infection in lower leaves and less infection in the younger leaves formed higher on the wheat plants.

In the absence of barberry or other alternate hosts, urediniospores are the only functional spores in the disease cycle of P. graminis. In tropical and subtropical climates, mycelium and urediniospores on volunteer wheat and noncrop grass hosts begin epidemics. Urediniospores are generally unable to survive harsh winter conditions. In the Northern Hemisphere, inoculum for spring wheat arrives from southern areas. In the Southern Hemisphere, urediniospores arrive from milder areas in the north. Occasionally, P. graminis can overwinter in wheat volunteers, noncrop grass hosts, and winter wheat, but usually only where snow cover insulates both the wheat leaves and the fungal mycelium. This is most likely to occur where winter wheat is planted directly into wheat stubble from the previous crop.

Urediniospores are produced approximately 7 to 15 days after infection, so there can be multiple generations of inoculum produced during a single growing season. One uredinium can produce at least 100,000 urediniospores. Explosive epidemics can occur during favorable environmental conditions, resulting in losses of 50 to 70% over a region.

Stem rust causes cereal yield losses in several ways. The fungus absorbs nutrients from the plant tissues that would be used for grain development in a healthy plant. As pustules break through the epidermal tissue, it becomes difficult for the plant to control transpiration, so its metabolism becomes less efficient. Desiccation or infection by other fungi and bacteria also can occur. Interference with the vascular tissues results in shriveled grains. Stem rust also can weaken wheat stems, so plants lodge, or fall over, in heavy winds and rain (Figure 19). Where severe lodging occurs, crops cannot be mechanically harvested.

Barberry eradication: Once the life cycle of P. graminis was determined, the potential effects of the removal of the barberry alternate host became clear (Figures 20, 21). An expensive and extensive barberry survey (Figure 22) and eradication program was initiated in 1918 in the U.S. (Figure 23) and continues to a limited extent today (Figure 24).

It was originally hoped that the program would eliminate stem rust as a significant disease in North America, because the basidiospores would have no barberry hosts to infect, and urediniospores could not usually survive harsh winter conditions. The importance of continental spread of stem rust epidemics was not understood until later. Urediniospores overwinter in wheat fields in the southern U.S. and northern Mexico and are then airborne northward via what is now called the "Puccinia Pathway" (Figure 25). If the weather is favorable for stem rust development in the South, urediniospores will arrive in time and in sufficient numbers to cause epidemics in northern wheat-growing areas.

Despite this problem, barberry eradication has had significant positive effects on the control of stem rust epidemics. First, it removed a significant, early source of inoculum. A single barberry plant can produce as many as 64 billion aeciospores. Second, it reduced the genetic variation in the fungal population by eliminating the sexual cycle, leaving only asexual urediniospores to maintain the fungus. Mutation is now the primary source of genetic variation. Consequently, there are no longer so many different races of wheat stem rust against which wheat breeders must seek resistance. Finally, epidemics are delayed by several weeks in many of the major wheat producing areas of the U.S. and Canada because aeciospores were released before the first arrival of urediniospores from the south.

Cultural practices It has long been known that moisture on leaves and excessive foliar nitrogen favor infections by rust fungi. Farmers consider these factors in spacing, row orientation, and fertilizer schedules. Recent changes in production practices may have effects on stem rust. In some areas, summer wheat crops are irrigated, which may increase the survival of infected volunteer plants. In addition, many farmers are practicing no-till or minimum tillage. This increases the probability that rust fungi may successfully overwinter in the protective layer of stubble from the previous crop.

Use of earlier-maturing wheat varieties in the central Great Plains of the U.S. has helped reduce the threat of stem rust epidemics. Modern wheat varieties in that region mature about 2 weeks earlier than older varieties. This limits the length of time for stem rust epidemics to develop in the central Great Plains as well as the numbers of urediniospores that can contribute to epidemics farther north.

Genetic resistance Genetic resistance is the most commonly used and the most effective means to control stem rust. Its success in North America is directly related to the reduced number of races present in the fungal population following the barberry eradication program. Because funding for the program has been reduced in recent years, scientists feared that the remaining barberry bushes will continue to spread into the wheat growing areas to serve both as a source of inoculum and as a means by which the fungus can complete its sexual cycle. Also, scientists realized that even in the absence of barberry, the currently used resistance genes should not be expected to remain effective indefinitely as new races of the fungus continue to arise by mutation. At least 50 distinct genes for race-specific (vertical) resistance to stem rust have been identified in wheat or transferred to wheat by wide crosses to wild relatives of wheat. Not all of these resistance genes are equally useful. Many were quickly discarded from wheat breeding programs, because virulent races that could overcome their resistance were found to be already prevalent in the fungus population. Others appeared to be widely effective when first used, but new virulent races of the fungus appeared within a few years of widespread use of the new resistance.

For reasons that we do not fully understand, a few genes for race-specific (vertical) resistance to stem rust in wheat remained highly effective for many years. The most successful of these was Sr31, a gene that occurs on a segment of a chromosome from rye that was transferred into wheat by a complicated process of interspecific hybridization. Wheat with Sr31 quickly became popular worldwide, because, in addition to Sr31, the rye chromosome segment also carried genes for increased grain yield as well as additional genes for resistance to other rust diseases. Since the 1980s, wheat varieties with Sr31 were widely grown in nearly every major wheat-producing region throughout the world other than Australia. The effectiveness of Sr31 was so great that wheat stem rust declined to almost insignificant levels nearly everywhere in the world by the mid-1990s.

Recently, the resistance of Sr31 was finally overcome. A new race of the wheat stem rust fungus highly virulent to wheat varieties with Sr31 was found in Uganda in 1999. The new race, tentatively designated Ug99, rapidly dominated the fungus population in Uganda and spread to Kenya and Ethiopia where it caused major epidemics. Within a few years, Ug99 was found in South Africa and in Yemen, from which it has spread to the north and east as far as Iran. It seems inevitable that Ug99 will soon invade one of the world's richest wheat producing areas in the Punjab of India. Previous examples of long distance dispersal of rust fungi include spread of a unique race of wheat stem rust from South Africa to Australia, spread of coffee rust from Africa to South America, and spread of southern corn rust from Central America to Africa. To make matters worse, the Ug99 lineage of the stem rust fungus has expanded its virulence through mutations that allow it to overcome the resistance of at least two other vertical resistance genes that wheat breeders have relied on for protection from stem rust in North America and many other parts of the world.

In response to the threat of impending wheat stem rust epidemics around the world, an international effort was organized in 2008 to reduce the vulnerability of the world's wheat crops to rust diseases. The organization, the Borlaug Global Rust Initiative, is coordinated by staff at Cornell University and includes research leaders from two international agricultural research centers, CIMMYT and ICARDA, the Food and Agriculture Organization of the United Nations, and the Agricultural Research Service of the U.S. Department of Agriculture. Primary efforts are concentrated on developing and deploying new effective resistance to wheat stem rust globally. Vertical resistance must be considered in the short term even though the durability of the resistance may be questionable. Combining two or more effective vertical resistance genes will provide a better chance for longer lasting resistance. For the long term, however, wheat breeders may rely more on minor genes with additive effects of partial resistance expressed primarily in adult plants (i.e., horizontal resistance). A number of high yielding wheat lines with moderate levels of horizontal resistance have already been developed at the International Center for Wheat and Maize Research (CIMMYT). These advanced lines are being intercrossed to produce improved wheat varieties combining as many as four or five horizontal resistance genes to effectively suppress stem rust epidemics. To preserve these effective combinations of horizontal resistance genes even when the Ug99 epidemics subside, it will be necessary to identify genetic markers for each of the genes so that breeders can continue to select for their presence even in the absence of disease.

Chemical control In some areas where disease pressure is high, fungicides are applied to wheat to control rust diseases. Fungicides that inhibit the synthesis of sterols [i.e., sterol biosynthesis inhibitors (SBIs) or demethylation inhibitors (DMIs)] are particularly effective, but the cost of application is generally prohibitive for routine use in most wheat-growing areas in the U.S.

Potential approaches to management Urediniospores infect wheat only through stomata. Scientists have studied how germinating urediniospores locate stomata on leaf surfaces (Figure 27). Although several factors are involved, the germ tube is able to detect the guard cells by their physical dimensions relative to the epidermal cells. Once a stoma is found, an appressorium is produced and infection begins. In the future, it may be possible to breed wheat resistant that is resistant to urediniospore infection because it has epidermal patterns that are not recognized by the fungus.

Stem rust is one of the major diseases of wheat and barley and, therefore, a potential threat to the world food supply. Wheat is the largest food crop in the world, and barley is the sixth largest. Together, they account for more than 25% of the world food supply. It is estimated that more than $5 billion are lost to cereal rusts (leaf rust, stem rust, and stripe rust) each year. Cereal rusts have probably been a problem since the first cereal crops were grown in the Fertile Crescent. Spores of P. graminis have been found in archeological sites in Israel dating from 1300 B.C. Wheat, barley, and barberry all originated in the Fertile Crescent, so this complex relationship in the stem rust life cycle has an ancient history.

Wheat stem rust was a serious problem in ancient Greece and Rome. Rust was observed and recognized as early as the time of Aristotle (384-322 B.C.). The ancient Romans sacrificed red animals such as dogs, foxes, and cows to the rust god, Robigo or Robigus, each spring during the festival called the Robigalia in hopes that the wheat crop would be spared from the ravages of the rust (Figure 28). This festival was incorporated into the early Christian calendar as St. Mark's Day or Rogation on April 25. Historical weather records suggest that a series of rainy years, in which rust would have been more severe and wheat harvests reduced, may have contributed to the fall of the Roman Empire.

Although the parasitic nature of stem rust was not known until the 1700s, farmers in Europe had recognized much earlier that barberry was somehow connected to stem rust epidemics in wheat. Laws banning the planting of barberry near wheat fields were first passed in Rouen, France, in 1660.

The Italian scientists Fontana and Tozzetti independently provided the first detailed descriptions of the stem rust fungus in wheat in 1767. Persoon named it Puccinia graminis in 1797. By 1854, the Tulasne brothers recognized that some autoecious (single host) rust fungi could produce as many as five spore stages. They were the first to link the red (urediniospore) and black (teliospore) stages as different spores of the same organism, but the remaining stages of P. graminis remained a mystery.

Anton deBary was puzzled by the lack of infection when basidiospores of P. graminis were placed on wheat plants. Using the farmers' belief that barberries increased wheat rust, he successfully inoculated barberries with the basidiospores and observed the remaining spore stages develop on the alternate host. Once the heteroecious nature of the life cycle was established, many other known rust fungi were discovered to be heteroecious, and their hosts could be paired up.

Both wheat and barberry plants were brought to North America by the European colonists. Barberry has a number of practical uses including a yellow dye from the bark, jams and wines from the berries, tool handles from the wood, and fast-growing, thorny hedges to help retain animals. As in Europe, farmers began to recognize the connection between barberry and stem rust epidemics in wheat. Barberry laws were enacted in several New England colonies in the mid-1700s. However, barberry continued to spread as pioneer farmers moved west. From farmyard plantings, barberry spread into fencerows and woodlots. Barberry bushes can be 3 m (9 ft) high and produce abundant berries that are attractive to birds and animals that feed on them and spread their seeds.

After the devastating 1916 North American stem rust epidemic, a cooperative state and federal barberry eradication program was established in 1918 (Figure 22). This program was partially motivated by the concern about food supplies during war. A "war against barberries" was established that enlisted help from the general population through radio and newspaper ads, extension pamphlets, and booths at fairs urging them to aid in the destruction of barberries. Even school children were encouraged to help find sites where barberry bushes existed (Figure 29). From 1975 through 1980, the program was gradually returned to the jurisdictions of various states. A federal quarantine is still maintained against sale of stem rust-susceptible barberry in states that were part of the barberry eradication program. A barberry testing program was established to ensure that only barberry species and varieties, such as the popular ornamental Japanese barberry, that are immune to stem rust will be grown in the quarantine area.

USDA-ARS Cereal Disease Lab Website: Home page: http://www.ars.usda.gov/main/site_main.htm?modecode=36-40-05-00

Black Stem Rust Biology and Threat to Wheat Growers (from a presentation to the Central Plant Board Meeting February 5-8, 2001, Lexington, KY). Cereal Disease Laboratory website, University of Minnesota.

Introduction to cereal rusts: http://www.ars.usda.gov/Main/docs.htm?docid=9854

Barberry information: http://www.ars.usda.gov/Main/docs.htm?docid=9747

Bushnell, W.R. and A.P. Roelfs, 1984. The Cereal Rusts. Vol. 1. Origins, Specificity, Structure, and Physiology. Academic Press, Orlando.

Carefoot, G.L. and E.R. Sprott, 1967. Famine on the Wind. Rand McNally and Co., Chicago.

Cook, R.J. and R.J. Veseth, 1991. Wheat Health Management. American Phytopathological Society Press, St. Paul, MN.

Dubin, H.J. and S. Rajaram, 1996. Breeding disease-resistant wheats for tropical highlands and lowlands. Annual Review of Phytopathology 34:503-526.

Large, E.C. 1940. Advance of the Fungi. Dover Publications, New York.

Leonard, K.J. and L.J. Szabo. 2005. Stem rust of small grains and grasses caused by Puccinia graminis. Molecular Plant Pathology 6:99-111.

Littlefield, L.J. 1981. Biology of the Plant Rusts: An Introduction. Iowa State University Press, Ames.

McIntosh, R.A. and G.N. Brown, 1997. Anticipatory breeding for resistance to rust diseases in wheat. Annual Review of Phytopathology 35:311-326.

Peterson, P.D. (ed.) 2001. Stem Rust of Wheat: From Ancient Enemy to Modern Foe. APS Press. St. Paul, MN.

Roelfs, A.P. 1982. Effects of barberry eradication on stem rust in the United States. Plant Disease 66:177-181.

Roelfs, A.P. 1989. Epidemiology of the cereal rusts in North America. Canadian Journal of Plant Pathology 11:86-90.

Roelfs, A.P., and W.R. Bushnell, 1985. The Cereal Rusts. Vol. 2. Diseases, Distribution, Epidemiology, and Control. Academic Press, Orlando.

Roelfs, A.P., R.P. Singh, and E.E. Saari, 1992. Rust Diseases of Wheat: Concepts and Methods of Disease Management. CIMMYT, Mexico, D.F.

Borlaug Global Rust Initiative: http://www.globalrust.org/

FAO website on the spread of race Ug99: http://www.fao.org/agriculture/crops/rust/stem/rust-report/stem-ug99racettksk/en/

Singh, R.P., D.P. Hodson, J. Huerta-Espino, Y. Jin, P. Njau, R. Wanyera, S.A. Herrera-Foessel, and R.W. Ward. 2008. Will stem rust destroy the world's wheat crop? Advances in Agronomy 98:272-309. (a pdf file of this reference can be found at http://ddr.nal.usda.gov/bitstream/10113/36520/1/IND44295123.pdf

Stone, M. 2010. Virulent new strains of rust fungus endanger world wheat. Microbe 5:423-428.http://www.microbemagazine.org/index.php/09-2010-home/2849-virulent-new-strains-of-rust-fungus-endanger-world-wheat

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Stem Cells – Resources for Research Ethics Education

Posted: August 28, 2016 at 12:50 pm

In recent years, biomedical research has been significantly altered by technologies for the derivation of human cell lines capable of differentiation into any of the cells of the human body. Such cells are sometimes called "pluripotent" because they have the power ("potency") to become many ("pluri-") different cells. It has long been known that such cells exist, but it wasnt until 1981 that stem cells were isolated from mouse embryos (Evans and Kaufman, 1981; Martin, 1981), and only in 1998 that the derivation of human embryonic stem cells was first reported (Thomson et al., 1998). This tool was quickly recognized as an opportunity to better understand normal and pathological human development, to identify and test new pharmacological therapies, and perhaps to even replace diseased tissues or organs. Many scientists viewed this as a potentially revolutionary approach to studying human biology. However, because a necessary first step was to use and destroy human embryos such research raised serious questions for some members of the public, as well as some scientists.

While most hESC scientists view the human embryo as human cells with great biological and scientific potential, there are many members of our society who hold religious beliefs that define the human embryo as equivalent to a human life. By this view, any harm or destruction of the human embryo is tantamount to harm or destruction of a human life. This perspective has become more than a matter of personal opinion. For many years now, under the Dickey amendment (1995), the U.S. Congress has agreed to federal restrictions on any research that would require harm or destruction of the human embryo. This restriction was partially lifted in 2001 by President Bushs announcement that research with stem cell lines existing as of August 9, 2001 could be eligible for federal funding.

Subsequently, President Obama annouced a new approach to approving stem cell lines for federal funding (Obama, 2009). The question now is not whether stem cell lines were created before a particular date, but whether or not those lines meet criteria that have been defined for ethically derived stem cell lines (NIH, 2009). While the result has been an increase in the number of stem cell lines approved for federal funding, it is noteworthy that the number of lines meeting these criteria is limited (NIH Human Embryonic Stem Cell Registry). In fact, many of the lines approved under the Bush policy are not acceptable under the Obama guidelines.

It would be a mistake to assume that religion is the only basis for arguments against hESC research. It is clear that some individuals and groups are motivated more by philosophical, political, or even economic arguments. However, whether based on religion or otherwise, most polls show that opponents to hESC research may represent a minority, but that minority is substantial in size and in impact (e.g., pollingreport.com).

Stem cells can be obtained from embryos, but embryos are only one of many potential sources. In the fetus, and even in an adult, stem cells can be found in many body tissues. The best known of these sources is bone marrow, in which stem cells are produced that are capable of differentiating into different types of blood ells. However, these stem cells are not pluripotent as defined above. Such cells are often called adult or tissue-specific stem cells. These cells have important, but restricted, clinical applications distinct from the wider range of possibilities with human embryonic stem cells (Wood, 2005).

Several sources of pluripotent stem cells have now been identified. One of these sources is based on the technology used to clone Dolly the sheep (Campbell et al., 1996), Snuppy the dog (Lee et al., 2005), and many other mammalian species. The first step to cloning these animals is a technique called Somatic Cell Nuclear Transfer (SCNT). SCNT in any species begins with an egg of that species from which the genetic material is removed. This egg can then be fused with an adult cell of the individual to be cloned. The result is an egg that now contains a full complement of DNA. Under appropriate laboratory conditions, that egg can be induced to divide as if it were a fertilized egg. If allowed to progress far enough, the resulting embryo can be implanted in the uterus of an individual of the same species, potentially resulting in the birth of a clone. However, it is also possible to allow the embryo to develop only for the purpose of harvesting stem cells rather than implantation. This source of stem cells is particularly important for stem cell research as well as potential therapies because of the opportunity to produce stem cells and differentiated cells that are genetically and immunologically matched to the adult donor.

Until 2005, researchers had been frustrated in their attempts to duplicate with human cells the same success achieved with SCNT in many other mammalian species. Some researchers were considering the possibility that SCNT in humans would be for all practical purposes impossible. This view was apparently proven wrong when the laboratory of Dr. Hwang Woo Suk published a report demonstrating successful derivation of stem cell lines from eleven separate cases of human SCNT (Hwang et al., 2005). Hwang, whose laboratory had cloned the first dog (Lee et al., 2005), was seen as so far ahead with SCNT that other laboratories around the world suspended attempts to achieve human SCNT, choosing instead to collaborate with Hwangs laboratory. Unfortunately, the story began to unravel in late 2005 and by the next year it was clear that the results announced in Dr. Hwangs paper were entirely falsified (Kennedy, 2006). Because researchers throughout the world had chosen to not pursue SCNT, this line of research was set back a year or more. It wasnt until 2008 that scientists at Stemagen successfully reported human SCNT (French et al., 2008)

Although SCNT has both scientific and therapeutic benefits, it still raises significant ethical questions, particularly because it depends on women who are willing and able to donate some of their eggs. Egg donation is not free of risk and, therefore, many bioethics committees and regulatory bodies have decided to err on the side of caution by prohibiting payment for eggs donated for the purposes of stem cell research. While on the one hand this position might be seen as paternalistic, the case can be made that any significant payment might lead those who are young or poor to overlook the possible risks of donation. The debate about payment is likely to continue, but it is clear that SCNT depends on a resource (human eggs) that is in limited supply and that can be obtained only through a time-consuming and invasive procedure.

An ongoing hope is that pluripotent cells might be found without the need for either human embryos or eggs. A number of reports have suggested that such cells might be found, for example, in amniotic fluid (De Coppi et al., 2007) and testes (Conrad et al., 2008). Another approach, reprogramming of adult cells, has been found to be far easier than expected and provisionally as good as or better than other sources of cells. In brief, cells (e.g., fibroblasts) are obtained from an individual, treated with a viral vector to introduce as few as 4 genes which, effectively, dedifferentiate (reprogram) the cells to become pluripotent stem cells (Takahishi et al., 2007; Yu et al., 2007). These cells are now commonly referred to as induced pluripotent stem (iPS) cells. Although these findings are intriguing, it remains to be seen whether the various alternative sources of pluripotent stem cells will prove to have the same qualities as the stem cells derived from human embryos (Hyun et al., 2007).

In just ten years (1998-2008), the field of human embryonic stem cell research evolved rapidly. Almost certainly, because of intense public scrutiny, the landscape for regulations and guidelines has also evolved rapidly. Unfortunately, the regulatory environment for this research varies not only across international borders, but significant differences are found even among the states of the United States. It is neither useful nor possible to describe regulations in each of these jurisdictions both because of extensive variation and because regulatory changes continue to be driven by changing public opinion and rapid advances in the sciences. However, a few examples are useful to illustrate the complex and often conflicting approaches to stem cell research across international and interstate borders.

Internationally, the environment for stem cell research ranges from a virtual prohibition to a near absence of restriction (Isasi and Knoppers, 2006). Several countries, including Austria, Norway, and Poland, have prohibited any human embryo research. Others, such as the U.S. and Germany, prohibit the use of federal funds for hESC research, but in the face of public pressure both countries have adopted national policies that allow the use of federal funds for stem cell lines created before August 2001 and May 2007, respectively. Finally, for all practical purposes, China and Singapore are examples of countries with relatively few restrictions on hESC research.

The variation across international borders in stem cell regulations should not be taken as a sign that the international stem cell community has been silent about the responsible conduct of stem cell research. The International Society for Stem Cell Research (ISSCR), (one of the leading international stem cell research organizations, has established a variety of guidelines that are now widely accepted throughout the stem cell research community (ISSCR, 2006). Key principles of these guidelines are:

While the U.S. has significant restrictions on the use of federal funds for stem cell research, such research is still permitted to the extent allowed under state laws. As with international stem cell regulations, tremendous variation can be found among different states (National Conference of State Legislatures, 2008). As of 2008, South Dakota prohibits hESC research, while some states (e.g., California, New York) have been not only permissive of stem cell research, but have approved significant public funding dedicated to hESC research.

The fact that some states are highly permissive of stem cell research does not mean that such research occurs in the absence of either regulations or guidelines. Nationally, guidance that is generally accepted has come from the National Academy of Sciences. Following their initial report (Committee on Guidelines for Human Embryonic Stem Cell Research, 2005), the NAS has published amendments in 2007 and 2008 (Human Embryonic Stem Cell Research Advisory Committee, 2007 and 2008). Two key points in those guidelines are:

One of the states that has been most receptive to hESC research is California. In 2004, a significant majority of California voters approved Proposition 71, creating a mechanism for allocating $3 billion for stem cell research over a 10-year period. This voter approved initiative also put in place a framework to promote scientific, legal and ethical oversight for stem cell research through the creation of the California Institute for Regenerative Medicine (CIRM). The resulting requirements for CIRM-funded research have generally been extended to all stem cell research in California. Under California law (California Institute for Regenerative Medicine, 2008), key requirements for stem cell research include requirements for review of the research by the equivalent of an ESCRO Committee, criteria for acceptable derivation of materials that are to be used for research use, and categories of research that are specifically prohibited.

Case Study #1

Clearly, from an ethical perspective, stem cell research constitutes one of the most complex of the numerous domains of research. Many considerations might be listed here, but three seem to be particularly noteworthy.

Chimeras: A chimera is defined in various ways, but the principle is that one organism consists of components that are demonstrably derived from two or more distinct species. The name chimera comes from a monster in Greek mythology that was a combination of different animals (typically a lion, goat, and snake). In biology, chimeras can now be formed either by inserting cells from one species into the adult of another species, or by creating an embryo that begins with cells from two or more species. In principle, it seems that our society already accepts the possibility of saving a childs life by replacing a defective heart with one that is non-human (e.g., a baboon heart, Altman, 1984), but we are much less comfortable with creating a non-human animal that might have human features (e.g., a human face, ear, or hand). Having the appearance of a human is problematic more because of our discomfort than because it necessarily raises some direct ethical dilemma. However, we have reason to be much more concerned about a human nervous system (i.e., do we have a risk of a non-human animal achieving levels of awareness and understanding that would make it sufficiently human to be deserving of human protections?) or human gametes (i.e., do we have a risk of two non-human animals reproducing with human gametes, thereby producing a human, or largely human, organism?). These questions are very much hypothetical and, if not impossible, highly improbable under the circumstance that the ethical, legal, scientific, and social environment is not one that favors these goals. Nonetheless, responsible science and policy require that one concern for reviewers of stem cell research is to address the potential risks with experiments that involve the mixing of stem cells from two or more species.

Clinical Trials: In the very near future, we are likely to see clinical trials based on reputable, pluripotent stem cell research. We are already seeing numerous stem cell "trials" worldwide that are arguably questionable, and sometimes criminal. By taking advantage of public awareness of and excitement about stem cell research, it is now possible to find groups that will offer to treat or cure almost anything in the context of a clinical "trial" that typically has no control group and for which participants must pay for participation. Payments for such "trials" are often on the order of $10,000 or more. Whether intentional or not, these trials are likely to be scams with little chance of success. Particularly under these circumstances, the stem cell field must meet a higher than average standard before approving the first clinical trials with this very new approach to treating disease. To do otherwise risks a backlash against all of stem cell research if initial trials unexpectedly result in a worsening of disease, serious side effects, or even death. All of these are possible outcomes no matter how much work has been done before the first trials in humans. Therefore to decrease that risk the scientific community can and should set a high bar both for the circumstances under which such a trial should be attempted and for the design of the research study to ensure the highest level of protections for informed consent and the welfare of the research participants.

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Sanford School of Medicine | USD – University of South Dakota

Posted: October 19, 2015 at 5:51 pm

Presenter: Michael Leon, PhD, Professor and Associate Dean, Department of Neurobiology and Behavior, Center for Autism Research and Translation, Center for the Neurobiology of Learning and Memory, The University of California, Irvine, California. Location: Sanford USD Medical Center Schroeder Auditorium Avera Education Center Classroom 2 (Avera sites dial in to 8103502) The VA Hospital Room 351, and registered video conferencing sites

Presenter: Sam Milanovich, MD, Assistant Professor, Department of Pediatrics, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota. Location: Health Science Center Room 106 Sioux Falls, SD Avera Education Center Classroom 2 (Avera sites dial in to 8103502) The VA Hospital Room 351, and registered video conferencing sites

Presenter: Jenny Miller, DC, Chiropractor/Acupuncture, Sioux Falls VA Hospital Location: VA Education Center, Building One, Room #123, Sioux Falls, South Dakota

Presenter: Jerome Freeman, MD, FACP, Professor and Chair, Department of Neurosciences, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota Location: Sanford USD Medical Center Schroeder Auditorium, Avera Education Center Classroom 3 (Avera sites dial in to 8103502) The VA Hospital Room 351, and registered video conferencing sites

Presenter: Anthony Sierra, MD, Clinical Professor, Department of Obstetrics and Gynecology, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota Location: Schroeder Auditorium, Sanford USD Medical Center Sioux Falls, South Dakota

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Sanford School of Medicine | USD - University of South Dakota

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A Natural Cure for Cancer?: THE FUTURIST Interviews Dr …

Posted: April 22, 2015 at 2:51 pm

When people come down with cancer, they submit to regimens of drugs and, if need be, harsh radiation treatments. But what if those patients could forego all of this and ward off their cancers with their own white blood cells? An experimental white-blood-cell-transfusion approach that Dr. Dipnarine Maharaj is developing might make that feasible.

Dr. Maharaj is a hematologist and oncologist at the South Florida Bone Marrow/Stem Cell Transplant Institute, a cancer treatment center that applies stem-cell therapies to cancers that have not responded well to other treatments. He is working on taking white blood cells from healthy donors and fusing them into patients with cancer, so that the transfused cells can stimulate the patients immune systems and enable them to ward off the cancers on their own.

His concept has precedentsdoctors successfully treat some other types of infections by transfusing white blood cellsand the initial experimental results are promising. He will need more time, however, and much more funding before his treatment approach is ready. Dr. Maharaj described his research to Rick Docksai, associate editor for THE FUTURIST, in the following interview.

Dr. Dipnarine Maharaj (photo credit: BMSCTI.org)

THE FUTURIST: Strengthening the body to wage its own fight against cancer, instead of relying on drugs or radiation, is certainly an appealing idea. What first drew you to it?

Dipnarine Maharaj: We asked the question, why is that some people get cancer and others dont? The answer is that someone whos got cancer, their immune system is broken down. So if the people who didnt get cancer, their immune systems are not broken down, how can we fix the cancer patients immune systems? Im a stem-cell physician, and weve had this procedure for many years where we use a patients own stem cells or the stem cells of a donor to reform the patients own immune system. Thats what actually helps to cure the cancer.

THE FUTURIST: How does your new approach go about boosting the bodys immune cells? What mechanisms are involved?

Maharaj: To cure cancer, we really have to repair the immune system. What were trying to do is apply that same knowledge to treat patients with solid tumors. The method Im using, were taking cells of the immune system from the donors, and were transfusing those cells into patients who have cancers. It is essentially a white-blood-cell transplant.

THE FUTURIST: How early in the progression of cancer would a patient need to be for the treatment to work effectively?

Maharaj: Were still under the clinical trials. But the best way I could answer that question is that the smaller the amount of disease at the time that it is done, the better the chance of a positive outcome.

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