Category Archives: California Stem Cells

Since the gene-editing potential of CRISPR systems was realized in 2013, they have been utilized in laboratories across the world for a wide variety of applications. When this gene-editing power is harnessed with the proliferative potential of stem cells, scientists level up their understanding of cell biology, human genetics and the future potential of medicine.

Thus far, the feasibility to edit stem cells using CRISPR technology has been demonstrated in two key areas: modeling and investigating human cell states and human diseases, and regenerative medicine.1 However, this has not been without challenges.

In this article, we explore some of the latest research in these spaces and the approaches that scientists are adopting to overcome these challenges. Deciphering cell-specific gene expression using CRISPRi in iPSC-derived neurons

Deploying CRISPR technology in iPSCs has been notoriously challenging, as Martin Kampmann, of the Kampmann lab at the University of California San Francisco, says: "CRISPR introduces DNA breaks, which can be toxic for iPSCs, since these cells have a highly active DNA damage response." To overcome the issue of toxicity, as a postdoc in the lab of Professor Jonathan Weissman, Kampmann co-invented a tool known as CRISPR interference (CRISPRi), where the DNA cutting ability of CRISPR/Cas9 is disabled.2 The "dead" Cas9 (or, dCas9) is still recruited to DNA as directed by a single guide RNA. It can therefore operate as a recruitment platform to target protein domains of interest to specific places in the genome.

CRISPRi permits gene repression at the transcription level, as opposed to RNAi which controls genes at the mRNA level. This allows researchers to repress certain genes within stem cells and decipher their function. Kampmann explains: "For CRISPRi, we target a transcriptional repressor domain (the KRAB domain) to the transcription start site of genes to repress their expression. This knockdown approach is highly effective and lacks the notorious off-target effects of RNAi-based gene knockdown."In a study published just last month, Kampmann's laboratory adopted a CRISPRi-based platform to conduct genetic screens in human neurons derived from iPSCs: "CRISPR-based genetic screens can reveal mechanisms by which these mutations cause cellular defects, and uncover cellular pathways we can target to correct those defects. Such pathways are potential therapeutic targets."3"We expressed the CRISPRi machinery (dCas9-KRAB) from a safe-harbor locus in the genome, where it is not silenced during neuronal differentiation. We also developed a CRISPRi construct with degrons, stability of which is controlled by small molecules. This way, we can induce CRISPRi knockdown of genes of interest at different times during neuronal differentiation."

Image: iPSC-derived neurons. Credit: Kampmann Lab, UCSF.Previous CRISPR-based screens have focused on cancer cell lines or stem cells rather than healthy human cells, thus limiting potential insights into the cell-type-specific roles of human genes. The researchers opted to screen in iPSC-derived neurons as genomic screens have revealed mechanisms of selective vulnerability in neurodegenerative diseases, and convergent mechanisms in neuropsychiatric disorders.

The large-scale CRISPRi screen uncovered genes that were essential for both neurons and iPSCs yet caused different transcriptomic phenotypes when knocked down. "For me, one of the most exciting findings was the broadly expressed genes that we think of as housekeeping genes had different functions in iPSCs versus neurons. This may explain why mutations in housekeeping genes can affect different cell types and tissues in the body in very different ways," says Kampmann. For example, knockdown of the E1 ubiquitin activating enzyme, UBA1, resulted in neuron-specific induction of a large number of genes, including endoplasmic reticulum chaperone HSPA5 and HSP90B1.

These results suggest that comprised UBA1 triggers a proteotoxic stress response in neurons but not iPSCs aligning with the suggested role of UBA1 in several neurodegenerative diseases. The authors note: "Parallel genetic screens across the full gamut of human cell types may systematically uncover context-specific roles of human genes, leading to a deeper mechanistic understanding of how they control human biology and disease."

Video credit: UCSF.

Developing and testing cell-based therapies for human disease using CRISPR

Several laboratories across the globe are in an apparent race to develop the first clinically relevant, efficacious and safe cell-based therapy utilizing CRISPR gene-editing technology.

Whilst a plethora of literature demonstrates the efficacy of CRISPR in editing the genome of mammalian cells in vitro, for in vivo application, particularly in humans, rigorous long-term testing of safety outcomes is required. This month, researchers from the laboratory of Hongkui Deng, a Professor at Peking University in Beijing, published a paper in The New England Journal of Medicine.4 The paper outlined their world-first study in which they transplanted allogenic CRISPR-edited stem cells into a human patient with HIV.

The rationale for the study stems back to the "Berlin patient", referring to Timothy Ray Brown who is one of very few individuals in the world that has been cured of HIV. Brown received a bone marrow transplant from an individual that carries a mutant form of the CCR5 gene. Under normal conditions, the CCR5 gene encodes a receptor on the surface of white blood cells. This receptor effectively provides a passageway for the HIV to enter cells. In individuals with two copies of the CCR5 mutation, the receptor is distorted and restricts strains of HIV from entering cells.

Deng and colleagues used CRISPR to genetically edit donor hematopoietic stem and progenitor cells (HSPCs) to carry either a CCR5 insertion or deletion. They were able to achieve this with an efficiency of 17.8%, indicated by genetic sequencing. The CRISPR-edited HSPCs were then transplanted into an HIV patient who also had leukaemia and required a bone-marrow transplant, with the goal being to eradicate HIV.

"The study was designed to assess the safety and feasibility of the transplantation of CRISPRCas9modified HSPCs into HIV-1positive patients with hematologic cancer," Deng says. He continues: "The success of genome editing in human hematopoietic stem and progenitor cells was evaluated in three aspects including editing persistence, specificity and efficiency in long-term engrafting HSPCs." Long-term monitoring of the HIV patient found that, 19 months after transplantation, the CRISPR-edited stem cells were alive however, they only comprised five to eight percent of total stem cells. Thus, the patient is still infected with HIV.

Despite the seemingly low efficiency in long-term survival, the researchers were encouraged by the results from the safety assessment aspect of the study: "Previously reported hematopoietic stem and progenitor cells-based gene therapies were less effective because of random integration of exogenous DNA into the genome, which sometimes induced acute immune responses or neoplasia," Deng says. "The apparent absence of clinical adverse events from gene editing and off-target effects in this study provides preliminary support for the safety of this gene-editing approach."

"To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPRCas9 system and improve the transplantation protocol," says Deng.

The marrying of CRISPR gene-editing and stem cell research isn't just bolstering therapeutic developments in HIV. An ongoing clinical trial is evaluating the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ HSPCs for the treatment of transfusion-dependent -thalassemia, a genetic blood disorder that causes hemoglobin deficiency.

The therapeutic approach known as CTX001 involves extracting a patients HSPCs and using CRISPR-Cas9 to modify the cells at the erythroid lineage-specific enhancer of the BCL11A gene. The genetically modified cells are then infused back into the patient's body, where they produce large numbers of red blood cells that contain fetal hemoglobin. Currently no results are available, but reports confirm that participants have been recruited on to the trial.

A bright future

Our understanding of cell biology and diseased states has been majorly enhanced by the combined use of CRISPR technology and stem cells. Whilst this article has focused on current study examples, Zhang et al.'s recent review provides a comprehensive view of the field and insights provided by earlier studies.5

In such review, the authors comment "Undoubtedly, the CRISPR/Cas9 genome-editing system has revolutionarily changed the fundamental and translational stem cell research." Solutions are still required to resolve the notorious off-target effects of CRISPR technology, to improve the editing efficiency as outlined by Deng and to exploit novel delivery strategies that are safe for clinical stem cell studies. Nonetheless, the future looks bright for CRISPR and stemcell-based research. In their review published this month, Bukhari and Mller say, "We expect CRISPR technology to be increasingly used in iPSC-derived organoids: protein function(subcellular localization, cell type specific expression, cleavage, and degradation) can be studied in developing as well as adult organoids under their native conditions."

References:

1. Jehuda, Shemer and Binah. 2018. Genome Editing in Induced Pluripotent Stem Cells using CRISPR/Cas9. Stem Cell Reviews and Reports. DOI: 10.1007/s12015-018-9811-3.

2. Qi et al. 2013. Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression. Cell. DOI: 10.1016/j.cell.2013.02.022

3. Tian et al. 2019. CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons. Neuron. https://doi.org/10.1016/j.neuron.2019.07.014.

4. Xu et al. 2019. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. The New England Journal of Medicine. DOI: 10.1056/NEJMoa1817426.

5. Zhang et al. 2019. CRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects. Molecular Therapy Nucleic Acids. DOI: 10.1016/j.omtn.

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Exploring the Latest in CRISPR and Stem Cell Research - Technology Networks

Gene editing will be tested in UW Medicine labs on kidney organoids tiny, kidney-like structures grown from stem cells as part of a federally funded effort to develop safe, effective genome editing technologies and therapies.

The National Institutes of Health today, Oct. 1, announced the next set of grant awards for the Somatic Cell Genome Editing consortium, created in 2018. Somatic cells make up the bodys tissues and organs, such as the lungs or blood, in contrast to reproductive cells, like fertilized eggs. Alterations made to somatic cell DNA are not passed down to the next generation.

In the latest round of SCGE funding, twenty-four grants, totaling about $89 million over four years, been awarded across the country. They will fund studies to address the promises and challenges of genome editing in the search for new treatment or cures for a number of genetic disorders.

The human genome contains thousands of genes responsible for making proteins. In many inherited disorders, a variation in the DNA code means that an important protein is not made, or is not made correctly. The missing or faulty protein could result in serious health problems. Genetic editing would aim to change the DNA to enable cells to make a sufficient amount of the proper protein.

For one of the new SCGE projects, collaborative research will take place between the University of Washington School of Medicine lab of kidney disease researcher Benjamin Beno Freedman, assistant professor of medicine, Division of Nephrology, and the University of California Berkeley lab of Jennifer Doudna, professor of molecular and cellular biology.

As a group, Freedman and his fellow researchers bring together expertise in kidney organoids, kidney cell biology, and kidney diseases. Their collaborators at UC Berkeley are leaders in the field of genome editing, including CRISPR-Cas9 gene editing technology to cut and paste portions of DNA in living cells.

Freedmans lab at the UW Medicine Institute for Stem Cell and Regenerative Medicine grow stem cell-derived organoids to study how kidney diseases begin and how they might be treated. Human kidney organoids and kidney-on-a-chip technologies (in which some functions of kidneys are simulated with living cells in tiny chambers) are providing useful medical information. For example, researchers have found new molecules that can reduce the signs of disease in these laboratory models.

Human kidney organoid showing podocytes (red) and proximal tubules (green) developed in the Freedman lab

Freedman explains the importance of exploring responsible gene-editing therapies for inherited kidney diseases: Genetic kidney diseases impact more than half a million people in the United States alone. If we can learn to safely repair the mutation that causes the disease, we can offer a way to treat patients that is much more effective than any current intervention.

Freedman emphasizes that dialysis and transplants two of the most common treatments for kidney diseases are expensive and hard on patients. Kidney transplants are in short supply; donor organs become available to less than 20 % of the patients who need them each year.

The shortcomings of dialysis and transplants make gene therapy an appealing area of research because it might get to the root of the problem.

One of the primary aims of the NIH-funded somatic cell genome editing explorations are to reduce the chances that gene editing produces unintended side effects that do more harm than good. In their collaborative project with UCBerkeley, the UW Medicine team will screen different gene therapies for their effects on normal kidney function and for risks of renal cancer or autoimmune disease.

Our hypothesis is that gene editing will cause adverse effects, but that these effects are predictable and controllable, says Freedman. Our goal is to prove this using laboratory models like organoids and kidneys on chips so we know the approach is safe before we ever involve a human patient.

Freedmans lab is in the Division of Nephrology, Department of Medicine, at the UW School of Medicine, and his lab is also part of the Kidney Research Institute, a collaboration between Northwest Kidney Centers and UW Medicine.

Joining Freedman on the UW Medicine research team are Institute for Stem Cell and Regenerative Medicine colleagues Hannele Ruohola-Baker, professor in biochemistry, and Julie Mathieu, assistant professor of comparative medicine, both at the UW School of Medicine.

Ruohola-Baker will investigate how genome-editing therapies affect cell metabolism. Mathieu adds CRISPR expertise to the UW research team. Several faculty members from other departments are also on the team.

How broad are the implications of developing responsible genome-editing methods?

This is a new paradigm for therapy development, says Freedman. Were looking at the kidney. But the liver, heart, and lungs all have similar challenges. Our hope is to create a model for doing this work in human organoids, which are faster and more humane than animal models, and can be more directly compared to human patients.

Genome editing has extraordinary potential to alter the treatment landscape for common and rare diseases, said Christopher P. Austin, director of the National Center for Advancing Translational Sciences and SCGE Program Working Group chair. The field is still in its infancy, and these newly funded projects promise to improve strategies to address a number of challenges, such as how best to deliver the right genes to the correct places in the genome efficiently and effectively. Together, the projects will help advance the translation of genome-editing technologies into patient care.

Nearly 40 million Americans have chronic kidney disease, a family of progressive conditions that can come with widespread health complications, including a higher risk for heart disease. When kidneys fail, the primary interventions, dialysis and kidney transplants, are not cures. These treatments come with significant side effects and a heavy economic burden. Medicare costs average $114 billion a year total for the care of the nations patients with kidney failure. Altogether, kidney disease is the ninth leading cause of death in the United States.

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Thatcher Heldring of the Institute for Stem Cell and Regenerative Medicine contributed to this news report.

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Genome editing to be tested in kidney organoids - UW Medicine Newsroom

SAN DIEGO--(BUSINESS WIRE)--Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced that it has opened for enrollment a Phase 1b expansion cohort of its Phase 1/2 clinical trial of cirmtuzumab, a ROR1-targeted monoclonal antibody, combined with ibrutinib, in patients with mantle cell lymphoma (MCL). The decision to open an expansion cohort in MCL of the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial was based on favorable interim results from the dose-finding cohort of the trial, including that the combination was well-tolerated and that complete responses were observed in two heavily pre-treated patients who had received and failed multiple chemotherapy regimens and an autologous transplant, as well as either an allotransplant or CAR-T therapy, prior to participating in this clinical trial.

In June, the Company presented interim data at the American Society of Clinical Oncology (ASCO) annual meeting, including the preliminary results from the first six patients with MCL treated in the CIRLL clinical trial. One patient with MCL, who had relapsed following an allogeneic stem cell transplant, experienced a confirmed complete response (CR) after three months of cirmtuzumab plus ibrutinib treatment, including complete resolution of a large mediastinal mass. This CR appears to be sustained and has been confirmed to be ongoing after completing 12 months of cirmtuzumab plus ibrutinib treatment. Following ASCO, a second confirmed CR occurred in a patient who had progressive disease after failing several different chemotherapy regimens, autologous transplant and CAR-T therapy. Additional data from this clinical trial will be presented at a future medical conference.

It is encouraging to see that the drug has been well tolerated as well as the early signal of efficacy of cirmtuzumab with ibrutinib in MCL, particularly the rapid and durable complete responses of the heavily pre-treated patients after three months of therapy, which is an unusually fast response in this patient population, said Hun Lee, M.D., Assistant Professor of Medicine in the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, who is an investigator on the CIRLL clinical trial.

The CIRLL clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM) and is being conducted in collaboration with the University of California San Diego (UC San Diego).

We are pleased to be opening the expansion cohort portion of the CIRLL clinical trial for patients with MCL, and continue to be encouraged by the interim results from this study for both patients with MCL and patients with chronic lymphocytic leukemia, for whom a randomized Phase 2 portion of the trial was opened in August, said James Breitmeyer, M.D., Ph.D., Oncternals President and CEO.

About the CIRLL Clinical Trial

The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Part 1 of the clinical trial was a Phase 1 dose-finding portion designed to determine the Phase 2 dose, or recommended dosing regimen (RDR). Part 2 is a Phase 1b expansion cohort to confirm the RDR. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL and MCL, in a collaboration with the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

ROR1 is a potentially attractive target for cancer therapy because it is an oncofetal antigen a protein that confers a survival and fitness advantage when reactivated and expressed by tumor cells. When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

About Oncternal Therapeutics

Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on developing product candidates for the treatment of cancers with critical unmet medical need. Oncternal focuses drug development on promising yet untapped biological pathways implicated in cancer generation or progression. The pipeline includes cirmtuzumab, an investigational monoclonal antibody designed to inhibit the ROR1 receptor, a type I tyrosine kinase-like orphan receptor, that is being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), and TK216, an investigational small-molecule compound that is designed to inhibit E26 transformation specific (ETS) family oncoproteins, that is being evaluated in a Phase 1 clinical trial for patients with Ewing sarcoma alone and in combination with vincristine chemotherapy. In addition, Oncternal has a program to develop a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors. More information is available at http://www.oncternal.com.

Forward-Looking Information

Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as may, will, should, expect, plan, anticipate, could, intend, target, project, contemplates, believes, estimates, predicts, potential or continue or the negatives of these terms or other similar expressions. These statements are based on the Companys current beliefs and expectations. Forward looking statements include statements regarding: Oncternals plans to present additional data from its ongoing Phase 1/2 clinical trial of cirmtuzumab; the expectation that Oncternal will be able to enroll patients into the Phase 1b expansion cohort; and Oncternals belief that favorable outcomes from the ongoing Phase 1 portion of the clinical trial support opening the Phase 1b portion. The inclusion of forward-looking statements should not be regarded as a representation by Oncternal that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in Oncternals business, including, without limitation: uncertainties associated with the clinical development and process for obtaining regulatory approval of cirmtuzumab and Oncternals other product candidates, including potential delays in the commencement, enrollment and completion of clinical trials; the Companys dependence on the success of cirmtuzumab and its other product development programs; the risk that interim results of a clinical trial do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; the risk that unforeseen adverse reactions or side effects may occur in the course of developing and testing product candidates such as cirmtuzumab and Oncternals other product candidates; the Companys limited operating history and that fact that it has incurred significant losses, and expects to continue to incur significant losses for the foreseeable future; risks related to the inability of Oncternal to obtain sufficient additional capital to continue to advance the development of cirmtuzumab and its other product candidates; and other risks described in the Companys prior press releases as well as in public periodic filings with the U.S. Securities & Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

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Oncternal Therapeutics Announces Opening of Phase 1b Expansion Cohort of Clinical Trial of Cirmtuzumab in Combination with Ibrutinib in Patients with...

Gabrielle Lurie / The Chronicle 2017

Stem cells under a microscope at Asterias Biotherapeutics.

How many clinics are there?

No one really knows for sure. Two scientists who have been observing the for-profit industry for years estimate there were 715 clinics operating as of 2017, and they believe there are more now. California has more clinics than any other state.

What treatments do the clinics offer?

None of the treatments are FDA approved. The therapies generally can be divided into three categories: stem cells drawn from a patients own fat; stem cells drawn from a patients bone marrow; and so-called amniotic stem cells, which come from donated amniotic fluid and tissue. There is some debate over whether the amniotic cells are stem cells at all.

In most cases, the stem cells are condensed and given to patients by injection.

What illnesses do the clinics claim to treat?

Bone marrow stem cells generally are given to people with joint or back pain. Clinics that sell fat and amniotic stem cell products market them for a wide variety of illnesses, including multiple sclerosis, Parkinsons disease, lung diseases and autism. There is no evidence that the products are effective at treating those maladies.

How much do the therapies cost?

Insurance almost never covers the cost of stem cell therapies provided by for-profit clinics. The out-of-pocket cost for patients can range from a few thousand dollars to more than $50,000 per treatment.

How are the clinics regulated?

The FDA issued guidelines in 2017 to clarify what types of stem cell products could be sold directly to consumers. Fat stem cell products were generally not allowed without specific FDA permission. Last year, the FDA requested injunctions to stop two major stem cell providers from selling fat-based products. One of those injunctions, against a clinic based in Florida, was approved earlier this year. The second injunction, against a network based in Southern California, awaits a court ruling.

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Q&A: California has more stem cell clinics than any state ...

Dr. Charity Dean of CDPH presenting at the Medical Board of California stem cell task force meeting.

This afternoon I attended and gave public comment at the Medical Board of California stem cell task force meeting on unproven stem cell clinics. There were about 40 people attending. In part this meeting is a consequence of the national governing organization of state medical boards, the Federation of State Medical Boards (FSMB) having worked on the stem cell clinic issue and crafting a policy on it. The FSMB was mentioned numerous times at the California meeting today.

Ive written before about how our California medical board has formed this task force to address the unproven stem cell issues. Its been slow going for this task force to get up and running, but it was great to see them in action and take part in this meeting. Drs. Howard R. Krauss and Randy W. Hawkins, task force Chairs, ran the meeting. You can see a pano picture of the start of the meeting that I took below, but not quite everyone had arrived at that point.

The meeting was very interesting, especially for what some might see as just another governmental agency meeting. In fact, it has some big implications for the clinics and even the stem cell field. You can see the agenda here. There were a number of presentations at the meeting including from Maria Milan, President of CIRM. My UC Davis colleague Dr. Merhdad Abedi also spoke. Both of their talks emphasized the rigorous stem cell-related clinic trials ongoing and in development, and the risks that come from deviating from standard clinical trial and GMP practices.

Dr. Charity Dean, Assistant Director of the California Department of Public Health (CDPH) also gave a very intriguing presentation. (Yes, Im officially a stem cell policy nerd.) Although there was quite a bit of focus on the different divisions within CDPH and how they may (or may not) have roles in overseeing stem cell clinics, the take home message seemed to be that this issue was definitely on their radar screen. Deans talk (and comments from her two CDPH colleagues) raised some other interesting points such as that even if a stem cell biologics manufacturer is located outside of California, if their product is shipped into California the CDPH still has some authority over it and licensing may be needed. Enforcement of an out of state supplier firm is more difficult though.

As to actual California firms, Dean noted that its not always clear who in the stem cell sphere needs a license. Also, interestingly, she pointed out that from a regulatory stand point there isnt such a thing defined as a stem cell clinic. It was clear that CDPH is actively monitoring the stem cell clinic situation, it tracks FDA warning letters, and it interfaces with the FDA.

Looking ahead, Drs. Krauss and Hawkins then talked about some ways the Medical Board of California might do more. They raised the idea of developing a guidance document for physicians and also producing public education materials. These could both be helpful, but I wonder whether the Board will actually take more direct action on the few physicians who are arguably running the riskiest clinics here in our state. Such a step would do the most to rein in the problem.

I was the first to give public comment after the presentations. I emphasized the large scope of the problem here in California where we have more than 100 unproven stem cell clinics. Im not going to rehash my comments, which may be familiar to those who read The Niche, but my main point was that the practices of many unproven California stem cell clinics significantly deviate from accepted standards of care and medical professionalism, putting patients at significant risks.

While some California stem cell clinics are FDA compliant (e.g. many but not necessarily all bone marrow firms), in my view others clearly arent, including in many cases adipose stem cell and perinatal firms. I also raised the concern about false marketing and failure to perform proper informed consent of patients/customers by some firms, based on my interactions with patients.

There were 3 other commenters. First, was Eric Robertson, a Parkinsons Disease patient advocate who is part of Summit for Stem Cell. He did a great job voicing his concern that the stem cell clinic problem could confuse the public and lead to negative repercussions.

The two other commenters were both physicians who use stem cells on patients, and one of them was actually associated with a clinic by name. Unfortunately, I didnt quite catch the doctors names. They expressed enthusiasm for the potential of bone marrow aspirate concentrate (BMAC) for various things including orthopedic conditions, especially the first of the two of them, who also spoke about anti-aging. The second doctor also was enthusiastic about PRP. In addition, he voiced the need for better standards and transparency by those using stem cells about what their products actually are. He indicated his view that some of them arent really stem cells and some are just dead cells. I definitely agree with him on the need for more clarity on whats actually being injected and consistency between that reality and the marketing. I actually thought that more clinic doctors would make public comment at the meeting, including some from adipose firms.

Overall, Id say the meeting was a positive development. I just dont know how much concrete action will come out of it and when. I also hope that other state medical boards will do more.

Note: this blog post represents my notes taken on the fly during the meeting so it may not be perfect, but to my knowledge it is accurate.

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Report from Medical Board of California meeting on stem ...

The online video seems to promise everything an arthritis patient could want.

The six-minute segment follows the format of a morning talk show, using a polished TV host to interview guests around a coffee table. Dr. Adam Pourcho extols the benefits of stem cells and regenerative medicine for healing joints without surgery. Pourcho, a sports medicine specialist, says he has used platelet injections to treat his own knee pain, as well as a tendon injury in his elbow. Extending his arm, he says, Its completely healed.

Brendan Hyland, a gym teacher and track coach, describes withstanding intense heel pain for 18 months before seeing Pourcho. Four months after the injections, he says, he was pain-free and has since gone on a 40-mile hike.

I dont have any pain that stops me from doing anything I want, Hyland says.

The videos cheerleading tone mimics the infomercials used to promote stem cell clinics, several of which have recently gotten into hot water with federal regulators, said Dr. Paul Knoepfler, a professor of cell biology and human anatomy at the University of California-Davis School of Medicine. But the marketing video wasnt filmed by a little-known operator.

It was sponsored by Swedish Medical Center, the largest nonprofit health provider in the Seattle area.

Swedish is one of a growing number of respected hospitals and health systems including the Mayo Clinic, the Cleveland Clinic and the University of Miami that have entered the lucrative business of stem cells and related therapies, including platelet injections. Typical treatments involve injecting patients joints with their own fat or bone marrow cells. Many hospitals, like Cedars-Sinai Medical Center in Los Angeles, offer extracts ofplatelets, the cell fragments known for their role in clotting blood.

Patients seek out regenerative medicine to stave off surgery, even though the evidence supporting these experimental therapies is thin at best, Knoepfler said.

Hospitals say theyre providing options to patients who have exhausted standard treatments. But critics suggest the hospitals are exploiting desperate patients and profiting from trendy but unproven treatments.

The Food and Drug Administration is attempting to shut down clinics that hawk unapproved stem cell therapies, which have been linked to several cases of blindness and at least 12 serious infections. Although doctors usually need preapproval to treat patients with human cells, the FDA has carved out a handful of exceptions, as long as the cells meet certain criteria, said Barbara Binzak Blumenfeld, an attorney who specializes in food and drug law at Buchanan Ingersoll & Rooney in Washington.

Hospitals like Mayo are careful to follow these criteria, to avoid running afoul of the FDA, said Dr. Shane Shapiro, program director for the Regenerative Medicine Therapeutics Suites at Mayo Clinics campus in Florida.

Expensive Placebos

While hospital-based stem cell treatments may be legal, theres no strong evidence they work, said Leigh Turner, an associate professor at the University of Minnesotas Center for Bioethics who has published a series of articles describing the size and dynamics of the stem cell market.

FDA approval isnt needed and physicians can claim they arent violating federal regulations, Turner said. But just because something is legal doesnt make it ethical.

For doctors and hospitals, stem cells are easy money, Turner said. Patients typically pay more than $700 a treatment for platelets and up to $5,000 for fat and bone marrow injections. As a bonus, doctors dont have to wrangle with insurance companies, which view the procedures as experimental and largely dont cover them.

Its an out-of-pocket, cash-on-the-barrel economy, Turner said. Across the country, clinicians at elite medical facilities are lining their pockets by providing expensive placebos.

Some patient advocates worry that hospitals are more interested in capturing a slice of the stem-cell market than in proving their treatments actually work.

Its lucrative. Its easy to do. All these reputable institutions, they dont want to miss out on the business, said Dr. James Rickert, president of the Society for Patient Centered Orthopedics, which advocates for high-quality care. It preys on peoples desperation.

In a joint statement, Pourcho and Swedish defended the online video.

The terminology was kept simple and with analogies that the lay person would understand, according to the statement. As with any treatment that we provide, we encourage patients to research and consider all potential treatment options before deciding on what is best for them.

But Knoepfler said the guests on the video make several unbelievable claims.

At one point, Dr. Pourcho says that platelets release growth factors that tell the brain which types of stem cells to send to the site of an injury. According to Pourcho, these instructions make sure that tissues are repaired with the appropriate type of cell, and so you dont get, say, eyeball in your hand.

Knoepfler, who has studied stem cell biology for two decades, said he has never heard of any possibility of growing eyeball or other random tissues in your hand. Knoepfler, who wrote about the video in February on his blog, The Niche, said, Theres no way that the adult brain could send that kind of stem cells anywhere in the body.

The marketing video debuted in July on KING-TV, a Seattle station, as part of a local lifestyles show called New Day Northwest. Although much of the show is produced by the KING 5 news team, some segments like Pourchos interview are sponsored by local advertisers and produced by another team, said Jim Rose, president and general manager of KING 5 Media Group.

After being contacted by KHN, Rose asked Swedish to remove the video from YouTube because it wasnt labeled as sponsored content. Omitting that label could allow the video to be confused with news programming. The video now appears only on the KING-TV website, where Swedish is labeled as the sponsor.

The goal is to clearly inform viewers of paid content so they can distinguish editorial and news content from paid material, Rose said. We value the publics trust.

Increasing Scrutiny

Federal authorities have recently begun cracking down on doctors who make unproven claims or sell unapproved stem cell products.

In October, the Federal Trade Commission fined stem cell clinics millions of dollars for deceptive advertising, noting that the companies claimed to be able to treat or cure autism, Parkinsons disease and other serious diseases.

In a recent interview Scott Gottlieb, the FDA commissioner, said the agency will continue to go after what he called bad actors.

With more than 700 stem cell clinics in operation, the FDA is first targeting those posing the biggest threat, such as doctors who inject stem cells directly into the eye or brain.

There are clearly bad actors who are well over the line and who are creating significant risks for patients, Gottlieb said.

Gottlieb, set to leave office April 5, said hes also concerned about the financial exploitation of patients in pain.

Theres economic harm here, where products are being promoted that arent providing any proven benefits and where patients are paying out-of-pocket, Gottlieb said.

Dr. Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, said there is a broad spectrum of stem cell providers, ranging from university scientists leading rigorous clinical trials to doctors who promise stem cells are for just about anything. Hospitals operate somewhere in the middle, Marks said.

The good news is that theyre somewhat closer to the most rigorous academics, he said.

The Mayo Clinics regenerative medicine program, for example, focuses conditions such as arthritis, where injections pose few serious risks, even if thats not yet the standard of care, Shapiro said.

Rickert said its easy to see why hospitals are eager to get in the game.

The market for arthritis treatment is huge and growing. At least 30 million Americans have the most common form of arthritis, with diagnoses expected to soar as the population ages. Platelet injections for arthritis generated more than $93 million in revenue in 2015, according to an article last year in The Journal of Knee Surgery.

We have patients in our offices demanding these treatments, Shapiro said. If they dont get them from us, they will get them somewhere else.

Doctors at the Mayo Clinic try to provide stem cell treatments and similar therapies responsibly, Shapiro said. In a paper published this year, Shapiro described the hospitals consultation service, in which doctors explain patients options and clear up misconceptions about what stem cells and other injections can do. Doctors can refer patients to treatment or clinical trials.

Most of the patients do not get a regenerative [stem cell] procedure, Shapiro said. They dont get it because after we have a frank conversation, they decide, Maybe its not for me.

Lots Of Hype, Little Proof

Although some hospitals boast of high success rates for their stem cell procedures, published research often paints a different story.

The Mayo Clinic website says that 40 to 70% of patients find some level of pain relief. Atlanta-based Emory Healthcare claims that 75 to 80% of patients have had significant pain relief and improved function. In the Swedish video, Pourcho claims we can treat really any tendon or any joint with PRP, or platelet-rich plasma injections.

The strongest evidence for PRP is in pain relief for arthritic knees and tennis elbow, where it appears to be safe and perhaps helpful, said Dr. Nicolas Piuzzi, an orthopedic surgeon at the Cleveland Clinic.

But PRP hasnt been proven to help every part of the body, he said.

PRP has been linked to serious complications when injected to treat patellar tendinitis, an injury to the tendon connecting the kneecap to the shinbone. In a 2013 paper, researchers described the cases of three patients whose pain got dramatically worse after PRP injections. One patient lost bone and underwent surgery to repair the damage.

People will say, If you inject PRP, you will return to sports faster, said Dr. Freddie Fu, chairman of orthopedic surgery at the University of Pittsburgh Medical Center. But that hasnt been proven.

A 2017 study of PRP found it relieved knee pain slightly better than injections of hyaluronic acid. But thats nothing to brag about, Rickert said, given that hyaluronic acid therapy doesnt work, either. While some PRP studies have shown more positive results, Rickert notes that most were so small or poorly designed that their results arent reliable.

In its 2013 guidelines for knee arthritis, the American Academy of Orthopaedic Surgeons said it is unable to recommend for or against PRP.

PRP is sort of a buyer beware situation, said Dr. William Li, president and CEO of the Angiogenesis Foundation, whose research focuses on blood vessel formation. Its the poor mans approach to biotechnology.

Tests of other stem cell injections also have failed to live up to expectations.

Shapiro published a rigorously designed study last year in Cartilage, a medical journal, that found bone marrow injections were no better at relieving knee pain than saltwater injections. Rickert noted that patients who are in pain often get relief from placebos. The more invasive the procedure, the stronger the placebo effect, he said, perhaps because patients become invested in the idea that an intervention will really help. Even saltwater injections help 70% of patients, Fu said.

A 2016 review in the Journal of Bone and Joint Surgery concluded that the value and effective use of cell therapy in orthopaedics remain unclear. The following year, a review in the British Journal of Sports Medicine concluded, We do not recommend stem cell therapy for knee arthritis.

Shapiro said hospitals and health plans are right to be cautious.

The insurance companies dont pay for fat grafting or bone-marrow aspiration, and rightly so, Shapiro said. Thats because we dont have enough evidence.

Rickert, an orthopedist in Bedford, Ind., said fat, bone marrow and platelet injections should be offered only through clinical trials, which carefully evaluate experimental treatments. Patients shouldnt be charged for these services until theyve been tested and shown to work.

Orthopedists surgeons who specialize in bones and muscles have a history of performing unproven procedures, including spinal fusion, surgery for rotator cuff disease and arthroscopy for worn-out knees, Turner said. Recently, studies have shown them to be no more effective than placebos.

Misleading Marketing

Some argue that joint injections shouldnt be marketed as stem cell treatments at all.

Piuzzi said he prefers to call the injections orthobiologics,noting that platelets are not even cells, let alone stem cells. The number of stem cells in fat and bone marrow injections is extremely small, he said. In fat tissue, only about 1 in 2,000 cells is a stem cell, according to a March paper in The Bone & Joint Journal. Stem cells are even rarer in bone marrow, where 1 in 10,000 to 20,000 cells is a stem cell.

Patients are attracted to regenerative medicine because they assume it will regrow their lost cartilage, Piuzzi said. Theres no solid evidence that the commercial injections used today spur tissue growth, Piuzzi said. Although doctors hope that platelets will release anti-inflammatory substances, which could theoretically help calm an inflamed joint, they dont know why some patients who receive platelet injections feel better, but others dont.

So, it comes as no surprise that many patients have trouble sorting through the hype.

Florida resident Kathy Walsh, 61, said she wasted nearly $10,000 on stem cell and platelet injections at a Miami clinic, hoping to avoid knee replacement surgery.

When Walsh heard about a doctor in Miami claiming to regenerate knee cartilage with stem cells, it seemed like an answer to a prayer, said Walsh, of Stuart, Fla. Youre so much in pain and so frustrated that you cling to every bit of hope you can get, even if it does cost you a lot of money.

The injections eased her pain for only a few months. Eventually, she had both knees replaced. She has been nearly pain-free ever since. My only regret, she said, is that I wasted so much time and money.

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Elite Hospitals Plunge Into Unproven Stem Cell Treatments ...

New research from the University of Southern California has come to light that fasting as little as eight (8) days a year could deliver significant health benefits, especially when it comes to stem cells.

Believe it or not, fasting two to four days at a time (every six months) causes stem cells to awaken from their normal dormant state, and start regenerating.

Essentially, researchers discovered that fasting helped eliminate damaged and older cells, allowing new healthier cells to replace them completely, effectively renewing the immune system.

This is one of the first times any natural intervention has ever been shown to trigger this self-renewal.

Going a bit deeper In mice and humans, white blood cell counts were significantly lowered after long periods without food. These bodies are vital to the human immune system.

But, when their numbers decline to a critical point, pathways for hematopoietic stem cells were switched on. These cells manage the immune system and generate new blood.

When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged, Valter Longo of the USC Davis School of Gerontology, said.

Fasting for an extended period of time (up to 48 to 96 hours) changes the human body to consume fat reserves, glucose (sugar), and ketones. Unhealthy white blood cells are also broken down, so that in part, their components can be reused for new, thriving cells.

This is considered to be a cell recycling of sorts.

After a period of fasting, the bodys immune system will generate new blood cells when nutrients begin flowing back into the body.

The main point of interest in this study at USC, they were committed to knowing what drives body systems to rebuild the cells.

To go further into the science a bit

The study found that Protein kinase A, an enzyme known to inhibit cell regeneration, was reduced in the systems of people who are fasting. Concentrations of a growth-factor hormone called IGF-1 were also lowered in those who have not eaten in days.

Important note: you will want to be careful if you decide to fast on only water for extended periods of time. To protect yourself, fasting for two to four days at a time should be done under medical supervision.

Another approach to fasting which has produced beneficial results is time restricted eating or intermittent fasting. This form of fasting involves eating in an 8 hour window and not eating during the remaining 16 hours.

This could be during a span from noon to 8:00 pm or 9:00 am to 5:00 pm. This time period will be completely up to you, just as long as you limit your intake to a single eight hour duration.

Youre not limited to the amount of water, and intermittent fasting is growing in popularity but is still considered a secret in the stem cell community.

Fasting has been a widely used approach for generations going back to early civilization, but either as a survival, ritualistic, or weight loss tactic.

But now, we have the research to support that fasting is an incredibly powerful stem cell boosting secret that can return powerful results.

After this study (and others) surfaced, we became inspired to see what other natural alternative secrets are out there.

In the end, we were able to gather and expand on 7 Secrets PROVEN to Grow More Stem Cells.

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Grow Stem Cells with Fasting - The Healing Miracle

Are you located in Lodi, California and need Stem Cells. Stem Cells may help you avoid having Surgery by simply coming to our Los Angeles Metro Area Stem Cell Sports and Regeneration Medicine Centers of Excellence in California.

A considerable amount of patients in California are turning to Stem Cell Therapy instead of surgery when their mobility and quality of life are severely affected by conditions or Injuries. Dennis M Lox M.D. specializes in progressive, innovative treatments that may be able to help you return to an active, fulfilling life in Lodi, California.

Dennis M Lox M.D. is a Specialist in Stem Cell Regenerative Medicine that focuses on Stem Cells and has been helping patients since 1990 to increase their quality of life by reducing their pain. He emphasizes non-surgical treatments and appropriate use of medications.

Stem Cells are extracted from ones own body fat or bone marrow. The Stem Cells are then concentrated and injected in to the injured area. The whole process can be done in one day making surgery a thing of the past.

We can even assist you with first class Limo Services, making your experience as comfortable and enjoyable as possible.

If you live in California and are looking in to having an alternative to Surgery Stem Cells may be able to help you. Please Contact Dennis M Lox M.D. at the Los Angeles Metro Area Stem Cells Sports and Regenerative Medicine Center of Excellence at (310) 975-7033 or fill out the form below and find out if Stem Cells can help you have a better life.

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Lodi, California Stem Cells, Stem Cells Lodi, California ...

Leaders of the California program say that what voters really care about are treatments for diseases, not what cell type is used. They say that from the outset the program was not restricted to the embryonic cells.

The commitment to voters was to pursue the very best cell type for each disease, said Robert N. Klein, the chairman of the California Institute for Regenerative Medicine, the agency that runs the program.

Still, the grant awards are likely to bolster one argument made by opponents of embryonic stem cell work: that such cells are not needed because treatments using adult cells are closer to fruition.

This is the stuff thats delivering for patients, said David Prentice, senior fellow for life sciences at the Family Research Council, an organization opposed to abortion and embryonic stem cell research.

The California grants are in a sense, not surprising, Mr. Prentice said.

Embryonic stem cells can grow easily in culture and can turn into virtually any type of tissue in the body. The hope is that the cells might be turned into heart cells, brain cells or other types of cells to repair damaged and diseased organs.

But the embryonic stem cells themselves can grow into tumors in the body, so the cells have to be first turned into pure preparations of specific types of cells.

Adult stem cells can be obtained from the human body and turned into a more limited range of tissues. But adult stem cells have been the subject of research for a longer time and, in the form of bone marrow transplants, are already used to treat a variety of diseases.

One project financed Wednesday would involve retrieving cardiac stem cells from a patients heart. The cells would be multiplied in culture and then put back into the heart to try to repair damage from a heart attack.

Dr. Eduardo Marbn of Cedars-Sinai Medical Center, who will lead the project, said embryonic stem cells turn into immature heart cells that might not help an adult heart. The last thing we want to do is grow rogue heart cells, Dr. Marbn said.

Still, one project awarded financing would use embryonic stem cells to make insulin-producing islet cells that would be implanted in the body to treat Type 1 diabetes. The $20 million for the project went to Novocell, a San Diego biotechnology company, and the University of California, San Francisco.

Other projects involving embryonic stem cells are intended to treat stroke, Lou Gehrigs disease and the eye disease called macular degeneration.

One project will use so-called induced pluripotent stem cells, which can be made from a patients own skin cells and have many of the properties of embryonic stem cells. Scientists at Stanford hope to harness those cells to treat a rare but debilitating skin disease called epidermolysis bullosa.

Two projects will essentially try to replicate the reported cure last year of a patient with AIDS. The patient, in Berlin, also had leukemia and got a bone marrow transplant to treat that disease. But the bone marrow donor had a genetic makeup making him naturally resistant to H.I.V.

For a given patient with AIDS it would be nearly impossible to find a donor that is both a good match and naturally resistant to H.I.V. infection. But the two research teams plan to take a patients blood-forming stem cells and inactivate a gene to make them resistant to H.I.V., then put them back in the body.

In addition to the $230 million being provided by California, the governments of Canada and Britain are together contributing $43 million because some of the research will be done in those countries.

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California Awards Grants for Research Projects in ...

Plant stem cells are innately undifferentiated cells located in the meristems of plants.[1] Plant stem cells serve as the origin of plant vitality, as they maintain themselves while providing a steady supply of precursor cells to form differentiated tissues and organs in plants.[2][not in citation given] Two distinct areas of stem cells are recognised: the apical meristem and the lateral meristem.

Plant stem cells are characterized by two distinctive properties, which are: the ability to create all differentiated cell types and the ability to self-renew such that the number of stem cells is maintained.[3] Plant stem cells never undergo aging process but immortally give rise to new specialized and unspecialized cells, and they have the potential to grow into any organ, tissue, or cell in the body.[2][not in citation given] Thus they are totipotent cells equipped with regenerative powers that facilitate plant growth and production of new organs throughout lifetime.[1][not in citation given]

Unlike animals, plants are immobile. As plants cannot escape from danger by taking motion, they need a special mechanism to withstand various and sometimes unforeseen environmental stress. Here, what empowers them to withstand harsh external influence and preserve life is stem cells. In fact, plants comprise the oldest and the largest living organisms on earth, including Bristlecone Pines in California, U.S. (4,842 years old), and the Giant Sequoia in mountainous regions of California, U.S. (87 meters in height and 2,000 tons in weight).[4] This is possible because they have a modular body plan that enables them to survive substantial damage by initiating continuous and repetitive formation of new structures and organs such as leaves and flowers.[1]

Plant stem cells are also characterized by their location in specialized structures called meristematic tissues, which are located in root apical meristem (RAM), shoot apical meristem (SAM), and vascular system ((pro)cambium or vascular meristem.)[5]

Traditionally, plant stem cells were thought to only exist in SAM and RAM and studies were conducted based on this assumption. However, recent studies have indicated that (pro)cambium also serves as a niche for plant stem cells: "Procambium cells fulfill the criteria for being stem cells since they have the capacity for long-term self renewal and being able to differentiate into one or more specialized cell types."[6][not in citation given]

Cambium is a type of meristem with thin walls which minutely exist in small populations within a plant. Due to this structural characteristic, once physical force is applied to it, it is easily damaged in the very process of isolation, losing its stem cell characteristics. Despite 160 years of biological effort to isolate and retrieve plant stem cells, none succeeded in the isolation due to the distinct structural characteristics of plant stem cell: "[t]he cambium consists of a few layers of narrow elongated, thin-walled cells, easily damaged during sampling." This highly vulnerable feature has made studies on cambial structure and ultrastructure difficult to achieve with conventional methods. Thus failure to isolate plant stem cells from meristematic tissues prompted scientists to administer plant cell culture by using callus (dedifferentiated cells) as an alternative to plant stem cells.

Callus, or dedifferentiated cells, are somatic cells that undergo dedifferentiation to give rise to totipotent embryogenic cells, which temporarily gains the ability to proliferate and/or regenerate an embryo. Since embryogenic cells were considered totipotent cells based on their ability to regenerate or develop into an embryo under given conditions, dedifferentiated cells were generally regarded as stem cells of plant: "we propose to extend the concept of stem cells to include embryogenic stem cells that arise from plant somatic cells. We examine the cellular, physiological and molecular similarities and differences between plant meristematic stem cells and embryogenic stem cells originating directly from single somatic cells."

Despite that callus exhibits a number of stem cell-like properties for a temporary period and that it has been cultured for useful plant compounds as an alternative source of plant stem cell, callus and plant stem cell are fundamentally different from each other. Callus is similar to plant stem cell in its ability to differentiate, but the two are different in their origin. While plant stem cell exists in the meristematic tissues of plant, callus is obtained as a temporary response to cure wounds in somatic cell.

Moreover, callus undergoes dedifferentiation as differentiated cells acquire ability to differentiate; but genetic variation is inevitable in the process because the cells consist of somatic undifferentiated cells from an adult subject plant. Unlike true stem cells, callus is heterogeneous. Due to this reason, continuous and stable cell division of callus is difficult. Hence a plant stem cell originated from cambium is an immortal cell while that from callus is a temporarily dediffertiated cell obtained from stimulating the somatic cell.

Furthermore, the ability to differentiate and proliferate is different that differences between plant stem cell and callus are prevalent in culture and research. Only plant stem cells embedded in meristems can divide and give rise to cells that differentiate while giving rise to new stem cells. These immortal cells divide infinitely.

Plant cells are cultured to acquire plant useful compounds. However cell cultures are often hindered by various factors especially if cell culture continues long-term. However, strong vitality and structural characteristics of plant stem cell overcome previous drawbacks to plant cell culture. Thus plant stem cell culture is the most ideal and productive method of cell culture and phytochemical production as cells are successfully mass cultured while maintaining quality.

Numerous medicines, perfumes, pigments, antimicrobials, and insecticides are derived from plant natural products. Cultured Cambial Meristematic Cells (CMC) may provide a cost-effective, environmentally friendly, and sustainable source of important natural products, including paclitaxel. Unlike plant cultivation, this approach is not subject to the unpredictability caused by variation in climatic conditions or political instability in certain part of the world. Also, CMCs from reference specifies may also provide an important biological tool to explore plant stem cell function.

In 2010, researchers from the Plant Stem Cell Institute (formerly Unhwa Institute of Science and Technology) presented their data to the world via Nature Biotechnology. Their research demonstrated the world's first cambial meristematic cell isolation. Due to the valuable and beneficial compounds for human health (i.e. paclitaxel) which are secreted by the CMC's, this technology is considered a serious breakthrough in plant biotechnology.[7][non-primary source needed]

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Plant stem cell - Wikipedia