Category Archives: Stem Cells

Those pesky wisdom teeth may be useful after all.

Researchers at the University of Pittsburgh School of Medicine say the dental pulp found in wisdom teeth is rich in stem cells that someday could be used to repair injured corneas.

Wisdom teeth have a pretty powerful population of stem cells, said Fatima Syed-Picard of Pitt's Department of Ophthalmology, lead author of a paper published Monday in the journal STEM CELLS Translational Medicine. It's not just your wisdom teeth; it's all your teeth. You can get similar stem cells from baby teeth.

The findings could lead to a new source of corneal transplant tissue to repair scarring of the cornea, the clear outermost layer of the eye, the researchers said. The scarring, caused by trauma, infections or genetic diseases, can result in permanent vision loss.

The team in the laboratory of ophthalmology professor James Funderburgh used pulp tissue from adult wisdom teeth obtained in routine extractions at Pitt's School of Dental Medicine.

Scientists cultured the extracted cells and turned them into keraocytes, which are cells that can heal the corneas. They then injected the cells into healthy mice to ensure they could work in a normal environment without being rejected, Syed-Picard said.

The method has not been tested in injured animals, and it could be years away from being tested in humans.

I'm confident that this will be easy to translate to humans in the near future, Syed-Picard said.

The Pitt scientists said they are looking at the wisdom teeth stem cells as a potential treatment to prevent corneal blindness, which afflicts millions of people worldwide.

The treatment of last resort is a corneal transplant using tissue from a deceased donor. Using stem cells from the patient's own tissue could help prevent rejection, they said.

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Dental stem cells valuable for cornea repair, University of Pittsburgh researchers find

MIAMI (PRWEB) February 24, 2015

In answer to industry-wide requests for more accessible solutions to stem cell procedures, Global Stem Cells Group, Inc. and Regenestem have announced the launch of two new stem cell harvesting and isolation kits.

The Regenestem BMAC 60 mL concentrating system is a high performing concentrating system for bone marrow aspirate. This kit come complete with a bone marrow filter, a bone marrow aspirating needle and a locking syringe to help maintain suction during the aspirating process. The BMAC 60 kit includes bone marrow concentrate up to 11 times the baseline values, to produce 6-8 mL BMC from a 60 mL sample of bone marrow aspirate.

The Regenestem 60 mL Adipose Derived Stem Cell (ADSC) Kit System includes all the tools and consumables for the extraction of adipose-derived stem cells from 60 mL of lipoaspirated fat. The ADSC kit is currently being used in clinical procedures for lung disease, intra-articular injections for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injections, stem cell enriched fat transfer, wounds, chronic ulcers and other chronic conditions. The enzymatic component used to obtain the stromal vascular fraction (SVF) is provided by Adistem.

The Regenestem ADSC Kit System is available in three versions:

Gold, to conduct in-office stem cell procedures with certified GMP components for reliable performance.

Platinum, with all the benefits of the basic (gold) kit plus a sterilized PRP close system with vortex engineering method to minimize platelet loss. One set of individually packed Tulip Gems instruments are added for safe and precise adipose tissue extraction.

Titanium, the perfect state-of-the-art deluxe kit system used by a growing number of regenerative medicine physicians and recognized as the perfect preparation for virtually all clinical applications. Built with Emcyte technology, the Regenestem Titanium kit has been independently reviewed and proven in various critical performance points that make a difference in patient outcomes.

The Titanium kit is currently being used in topical procedures such as intra-articular injection for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injection, stem cell enriched fat transfer, wounds chronic ulcers among other chronic conditions.

According to Global Stem Cells Group CEO Benito Novas, the entire Global Stem Cells Group faculty and scientific advisory board worked together to develop the kits.

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Global Stem Cells Group, Inc. Announces Launch of New Stem Cell Harvesting Products

Researchers from Cambridge University and Israels Weizmann Institute of Science are claiming a stem cell research breakthrough that would allow a baby to be created from the skin cells from two adults, no matter their gender. This potentially allows for infertile couples to have their own children without resorting to sperm or egg donors, and may provide the means for same sex couples to produce their own babies.

Previously only successful in experiments on mice, the new research has been conducted on human cells for the first time. In this study, the researchers paired stem cell lines from embryos with the skin of a range of different adults, with the resultant cells compared to aborted fetuses to determine an identical match.

Techniques devised to create same-sex offspring are not new. Some experiments involve the manipulation of fibroblasts in mice resulting in offspring with the genetic traits of multiple male mice, whilst others have used bone marrow stem cells extracted from males to trigger spermatogonia.

However, in this latest research, stem cells and adult human skin have been combined for the first time to create an entire new germ-cell line (that is, cells that will become embryos). Derived from ten different donor sources, the new germ-cell lines were created from 10 different donor sources five embryos and five adults.

Intrinsic to this pairing was the SOX17 gene. A master gene, SOX17 usually works to direct stem cells to be programmed to become whatever organs or body parts are required in other research this techniques has been used to create lung, gut, and pancreas cells.

The manipulation of the gene to be part of a primordial germ cell specification (that is, direct it to create cells that will become an entire human), however, is a new development pioneered by the team and has allowed them to follow this discovery with actually making primordial germ cells in the lab. This stage in a babys development is known as "specification", and once primordial germ cells become specified, they continue to develop inexorably toward precursor sperm or ova cells.

Creating human egg and sperm cells from the skin of two adults of the same gender immediately raises the possibility of same sex couples procreating and offering an alternate pregnancy path for infertile couples. Of course, it also opens the door to a new minefield of ethical and moral implications, but the researchers note that many people may potentially benefit from the technique.

The results of the research were published in the online journal Cell.

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Stem cell breakthrough may allow same gender couples to create babies

Durham, NC (PRWEB) February 23, 2015

Recent research aimed at finding a treatment for a common form of blindness could give new meaning to the term eye teeth. In a study in mice published in STEM CELLS Translational Medicine, researchers at the University of Pittsburgh show how stem cells harvested from teeth extracted during routine dental procedures can potentially be used to restore sight in those suffering from corneal blindness.

Corneal blindness afflicts millions of individuals worldwide. It occurs when the cornea becomes scarred and cloudy and light cannot penetrate the eye to reach the light-sensitive retina. Since corneal scarring is largely irreversible, the most common method of treatment is to graft a new cornea using tissue taken from cadavers. Given that there is a worldwide donor shortage and that many grafts are eventually rejected because they are not the patients own tissue, researchers have been looking for a new source for such tissue or a new way to regenerate the patients own cornea. (The current failure rate of corneal grafts is about 38 percent after 10 years, primarily due to tissue rejection.)

The University of Pittsburgh team, led by James L. Funderburgh, Ph.D., and Fatima Syed-Picard, Ph.D., both in the Department of Ophthalmology, decided to focus on adult dental pulp stem cells (DPSC) as a possible solution.

If we could generate an engineered cornea using autologous cells, which are the patients own cells, and then use that to replace scarred tissue, we could bypass the limitations of current treatments, Dr. Funderburgh explained. We thought dental pulp might be the answer, as other studies have proven that DPSCs can differentiate into various other cells and they already have a similarity to cornea tissue as they both develop in the embryo stage from the cranial neural crest, he added. That led us to believe that we might induce DPSCs to become corneal cells, too.

The team began by collecting DPSCs from molar teeth discarded after routine extractions at the universitys dental school and then treated the cells in a special solution that caused them to differentiate into corneal cells, or keratocytes. When they tested the DPSC-generated keratocytes they found they had the same properties as those grown naturally in the human eye.

They then seeded the cells onto a corneal shaped nanofiber substrate to see if they could engineer corneal tissue. Four weeks later, the cells had grown into a structure that mimicked the complex organization of an actual cornea.

Their final task was to evaluate how the DPSC-generated keratocytes would perform by labelling them with a dye (for tracking purposes) and then injecting them into the right eyes of mice. (The left eye of each animal was injected with medium only, as a control.) When they tested the mices eyes five weeks later, they found that the DPSC-generated keratocytes had remained in the corneas and behaved similar to natural keratocytes. Their corneas were clear, and there were no signs of rejection.

These studies provide promising data on the potential translation of DPSC as an autologous cell source for regenerative corneal therapies and possibly more, Dr. Funderburgh concluded.

This study provides promising data on the use of adult dental pulp cells for personalized regenerative medicine to treat corneal blindness, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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Stem Cells from Pulled Teeth Might Yield a Cure for Blindness

Stem cells from the dental pulp of wisdom teeth can be coaxed to turn into cells of the eye's cornea and could one day be used to repair corneal scarring due to infection or injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in STEM CELLS Translational Medicine, indicate they also could become a new source of corneal transplant tissue made from the patient's own cells.

Corneal blindness, which affects millions of people worldwide, is typically treated with transplants of donor corneas, said senior investigator James Funderburgh, Ph.D., professor of ophthalmology at Pitt and associate director of the Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, a joint program of UPMC Eye Center and the McGowan Institute for Regenerative Medicine.

"Shortages of donor corneas and rejection of donor tissue do occur, which can result in permanent vision loss," Dr. Funderburgh said. "Our work is promising because using the patient's own cells for treatment could help us avoid these problems."

Experiments conducted by lead author Fatima Syed-Picard, Ph.D., also of Pitt's Department of Ophthalmology, and the team showed that stem cells of the dental pulp, obtained from routine human third molar, or wisdom tooth, extractions performed at Pitt's School of Dental Medicine, could be turned into corneal stromal cells called keratocytes, which have the same embryonic origin.

The team injected the engineered keratocytes into the corneas of healthy mice, where they integrated without signs of rejection. They also used the cells to develop constructs of corneal stroma akin to natural tissue.

"Other research has shown that dental pulp stem cells can be used to make neural, bone and other cells," Dr. Syed-Picard noted. "They have great potential for use in regenerative therapies."

In future work, the researchers will assess whether the technique can correct corneal scarring in an animal model.

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The above story is based on materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Materials may be edited for content and length.

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Wisdom teeth stem cells can transform into cells that could treat corneal scarring

CryoSave, part of ESPERITE, is the only private cord blood bank sponsoring a GCPclinical trial according to GMP-ATMP international guidelines

CryoSave leads and sponsors a multicentre clinical trial following GCP-ICHstandards, for investigation of new treatment of Cerebral Palsy using dual infusionof two types of stem cells derived from umbilical cord blood and cord tissueprocessed by CryoSave

Geneva, Switzerland - 23 February 2015

The clinical trial aims to demonstrate safety and preliminary efficacy of sequential intravenousinfusion of the ex vivo expanded mesenchymal stem cells (MSC) derived from cord tissue and thecord blood stem cells. The study will use, for the first time in clinical research, autologous MSC

derived from cryopreserved cord tissue. The clinical trial, sponsored by CryoSave, will be performedin collaboration with Professor Manuel Ramrez Orellana, the Principal Investigator, and ProfessorLuis Madero, the Clinical Supervisor from the University Hospital Nio Jesus in Madrid, Spain.

Cerebral Palsy is a devastating disease diagnosed in 1 per 326 children according to CDC, with noavailable treatment. 17 Million people worldwide live affected by cerebral Palsy (CPIRF). 26 BillionUSD are spent every year to accommodate the life of these patients in the US (WHO).

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ESPERITE (Euronext ESP) pioneers first treatment worldwide of Cerebral Palsy using two types of stem cells

PRESS RELEASE

TiGenix's Phase III trial design

for Cx601 endorsed by President-Elect of ECCO

Leuven (BELGIUM) - 23 February, 2015 -TiGenix NV (Euronext Brussels: TIG), an advanced biopharmaceutical company focused on developing and commercialising novel therapeutics from its proprietary platform of allogeneic expanded adipose-derived stem cells in inflammatory and autoimmune diseases, announced today that Dr Julian Pans, a leading clinical specialist in inflammatory bowel disease, endorsed the design of the Company's Phase III trial of Cx601 for the treatment of complex perianal fistulas in patients with Crohn's disease during his presentation last week at the 10th Annual Congress of the European Crohn's and Colitis Organisation (ECCO) held in Barcelona, Spain.

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASCs) delivered locally through intra-lesional injection that is being developed for the treatment of perianal fistulas in Crohn's disease patients. Such fistulas cause severe complications and are difficult to manage, and have a significant negative impact on patient quality of life and psychological well-being. There is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognising the debilitating nature of the disease and the lack of treatment options.

TiGenix is conducting a randomised, double-blind, placebo-controlled Phase III trial in Europe and Israel designed to comply with the requirements laid down by the European Medicines Agency (EMA). This pivotal study, codenamed 'ADMIRE', has recruited 289 patients across 52 centres in 7 European countries and Israel. The results of the study will be available in the third quarter of 2015 and, if positive, will allow TiGenix to submit a request for marketing authorisation to the EMA early in 2016.

Dr. Julian Pans, who is Head of the Gastroenterology Department, Head of the Inflammatory Bowel Diseases Unit, and Associate Professor of Medicine at the Hospital Clnic of Barcelona, President-elect of ECCO and Chairman of the TiGenix ADMIRE Scientific Advisory Board, made his comments during a presentation last week at the Annual Congress of ECCO in a session entitled, 'Mesenchymal Stem Cells in Inflammatory Bowel Disease: promises and pitfalls'.

"I strongly believe that there are not in general adequately designed and controlled studies of the role of stem cells in the treatment of perianal fistulas in Crohn's disease patients," Dr. Panes said. "In the pivotal Phase III ADMIRE trial of TiGenix, we finally have the robust, controlled study that we have been waiting for."

"The positive evaluation of our Phase III study by Dr. Pans is strong recognition of the quality of our study design", commented Dr. Marie-Paule Richard, Chief Medical Officer at TiGenix. "We remain committed to bringing this new treatment to the thousands of patients who suffer from this debilitating condition".

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TiGenix: TiGenix's Phase III trial design for Cx601 endorsed by President-Elect of ECCO

Adult stem cells are flexible and can transform themselves into a wide variety of special cell types. Because they are harvested from adult organisms, there are no ethical objections to their use, and they therefore open up major possibilities in biomedicine. For instance, adult stem cells enable the stabilization or even regeneration of damaged tissue. Neural stem cells form a reservoir for nerve cells. Researchers hope to use them to treat neurodegenerative disorders such as Parkinson's and Alzheimer's disease. Tbingen researchers led by Professor Olga Garaschuk of the University of Tbingen's Institute for Physiology, working with colleagues from Yale University, the Max Planck Institute of Neurobiology in Martinsried and the Helmholtz Center in Munich, studied the integration of these cells into the pre-existing neural network in the living organism. The results of their study have been published in the latest edition of Nature Communications.

There are only two places in the brains of adult mammals where stem cells can be found -- the lateral ventricles and the hippocampus. These stem cells are generating neurons throughout life. The researchers focused on a stem cell zone in the lateral ventricle, from where progenitors of the nerve cells migrate towards the olfactory bulb. The olfactory nerves which start in the nasal tissue run down to this structure, which in mice is located at the frontal base of the brain. It is there that the former stem cells specialized in the task of processing information on smells detected by the nose. "Using the latest methods in microscopy, we were for the first time able to directly monitor functional properties of migrating neural progenitor cells inside the olfactory bulb in mice," says Olga Garaschuk. The researchers were able to track the cells using special fluorescent markers whose intensity changes according to the cell's activity.

The study showed that as little as 48 hours after the cells had arrived in the olfactory bulb, around half of them were capable of responding to olfactory stimuli. Even though the neural progenitor cells were still migrating, their sensitivity to odorants and their electrical activity were similar to those of the surrounding, mature neurons. The mature pattern of odor-evoked responses of these cells strongly contrasted with their molecular phenotype which was typical of immature, migrating neuroblasts. "Our data reveal a remarkably rapid functional integration of adult-born cells into the pre-existing neural network," says Garaschuk, "and they show that sensory-driven activity is in a position to orchestrate their migration and differentiation as well as their decision of when and where to integrate."

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Stem cell specialization observed in the brain

Under normal conditions, many of the different types of tissue-specific adult stem cells, including hematopoietic stem cells, exist in a state or dormancy where they rarely divide and have very low energy demands. "Our theory was that this state of dormancy protected hematopoietic stem cells from DNA damage and therefore protects them from premature aging," says Dr. Michael Milsom, leader of the study.

However, under conditions of stress, such as during chronic blood loss or infection, hematopoietic stem cells are driven into a state of rapid cell division in order to produce new blood cells and repair the damaged tissue. "It's like forcing you out of your bed in the middle of the night and then putting you into a sports car and asking you to drive as fast as you can around a race circuit while you are still half asleep," explains Milsom. "The stem cells go from a state of rest to very high activity within a short space of time, requiring them to rapidly increase their metabolic rate, synthesize new DNA and coordinate cell division. Suddenly having to simultaneously execute these complicated functions dramatically increases the likelihood that something will go wrong."

Indeed, experiments described in the study show that the increased energy demands of the stem cells during stress result in elevated production of reactive metabolites that can directly damage DNA. If this happens at the same time that the cell is trying to replicate its DNA, then this can cause either the death of the stem cell, or potentially the acquisition of mutations that may cause cancer.

Normal stem cells can repair the majority of this stress-induced DNA damage, but the more times you are exposed to stress, the more likely it is that a given stem cell will inefficiently repair the damage and then die or become mutated and act as a seed in the development of leukemia. "We believe that this model perfectly explains the gradual accumulation of DNA damage in stem cells with age and the associated reduction in the ability of a tissue to maintain and repair itself as you get older," Milsom adds.

In addition, the study goes on to examine how this stress response impacts on a mouse model of a rare inherited premature aging disorder that is caused by a defect in DNA repair. Patients with Fanconi anemia suffer a collapse of their blood system and have an extremely high risk of developing cancer. Mouse models of Fanconi anemia have exactly the same DNA repair defect as found in human patients but the mice never spontaneously develop the bone marrow failure observed in nearly all patients.

"We felt that stress induced DNA damage was the missing ingredient that was required to cause hematopoietic stem cell depletion in these mice," says Milsom. When Fanconi anemia mice were exposed to stimulation mimicking a prolonged viral infection, they were unable to efficiently repair the resulting DNA damage and their stem cells failed. In the same space of time that normal mice showed a gradual decline in hematopoietic stem cell numbers, the stem cells in Fanconi anemia mice were almost completely depleted, resulting in bone marrow failure and an inadequate production of blood cells to sustain life.

"This perfectly recapitulates what happens to Fanconi anemia patients and now gives us an opportunity to understand how this disease works and how we might better treat it," commented Milsom.

Prof. Dr. Andreas Trumpp, director of HI-STEM and head of the Division of Stem Cells and Cancer at the DKFZ believes that this work is a big step towards understanding a range of age-related diseases. "The novel link between physiologic stress, mutations in stem cells and aging is very exciting," says Trumpp, a co-author of the study. "By understanding the mechanism via which stem cells age, we can start to think about strategies to prevent or at least reduce the risk of damaged stem cells which are the cause of aging and the seed of cancer."

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The above story is based on materials provided by German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). Note: Materials may be edited for content and length.

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A good night's sleep keeps your stem cells young

19 hours ago Stem cells can be specifically distinguished from mature neural cells within a neurosphere using the novel fluorescent label CDy5 (red), with nuclei (blue) and cytosol (green). Credit: A*STAR Singapore Bioimaging Consortium

A labeling compound identified at A*STAR that specifically marks neuronal stem cells is not only a useful research tool, but could also assist clinical efforts to repair neurological damage in patients.

Even as adults, we retain reservoirs of neural stem cells that can develop into mature replacements for dead or damaged neurons. However, these reserves are relatively small, and insufficient for repairing severe injuries to the brain or spinal cord. Larger numbers of these stem cells could potentially be grown in culture dishes, but to do so researchers would need to be able to separate them from mature, fully developed neurons that are ineffective for tissue repair.

Young-Tae Chang's group at the A*STAR Singapore Bioimaging Consortium is looking for a way "to find and isolate neural stem cells using fluorescent dyes, to then grow them in larger numbers to treat neuronal damage or neurodegenerative diseases."

Chang and Sohail Ahmed of the A*STAR Institute of Medical Biology recently succeeded in identifying such a dye. One of the challenges in cultivating neural stem cells is that although some will divide 'symmetrically' to yield two new stem cells, others divide 'asymmetrically' to produce one stem cell and one mature neuron or glial cells.

Reliably identifying true stem cells with existing dyes has proved challenging to date. "These dyes just diffuse out into both cells," says Chang. He and Ahmed therefore screened a large library of fluorescent chemical compounds in search of a dye that consistently remains stem-cell-specific.

One molecule, which the researchers named CDy5, proved particularly promising. Cultured neural stem cells gradually form structures called neurospheres, composed of both stem cells and neural cells of various stages of maturity. After labeling neurospheres with CDy5, Chang and Ahmed separated out the brightly labeled cells from the dimly labeled ones. Strikingly, cells that were strongly labeled by CDy5 were ten times more likely to form neurospheres (see image). Experiments with single cells showed that this dye remained stem-cell-specific even during asymmetric division, and the researchers subsequently learned that CDy5 forms a strong chemical bond with a protein that is exclusively active in neural stem cells.

Chang intends to use CDy5 to identify culture conditions that either help stem cells maintain their identity or prompt their development into mature nervous tissue. He is also keen to make this tool available to other groups. "I will distribute CDy5 to whoever is interested in using the probe and am excited to see what kinds of new applications or discoveries result," he says.

Explore further: Unlocking the potential of stem cells to repair brain damage

More information: Yun, S.-W., Leong, C., Bi, X., Ha, H.-H., Yu, Y. H. et al. "A fluorescent probe for imaging symmetric and asymmetric cell division in neurosphere formation." Chemical Communications 50, 74927494 (2014). dx.doi.org/10.1039/c4cc02974g

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Scientists learn to monitor neural stem cells that might help repair neurological damage