ScienceDaily (Sep. 11, 2012) By including chemotherapy as a conditioning regimen prior to treatment, researchers have developed a refined gene therapy approach that safely and effectively restores the immune system of children with a form of severe combined immunodeficiency (SCID), according to a study published online September 11 in Blood, the Journal of the American Society of Hematology (ASH).

SCID is a group of rare and debilitating genetic disorders that affect the normal development of the immune system in newborns. Infants with SCID are prone to serious, life-threatening infections within the first few months of life and require extensive treatment for survival beyond infancy.

Adenosine deaminase (ADA) deficiency, which accounts for approximately 15 percent of all SCID cases, develops when a gene mutation prohibits the production of ADA, an enzyme that breaks down toxic molecules that can accumulate to harmful levels and kill lymphocytes, the specialized white blood cells that help make up the immune system. In its absence, infants with ADA-deficient SCID lack almost all immune defenses and their condition is almost always fatal within two years if left untreated. Standard treatment for ADA-deficient SCID is a hematopoietic stem cell transplant (HSCT) from a sibling or related donor; however, finding a matched donor can be difficult and transplants can carry significant risks. An alternate treatment method, enzyme replacement therapy (ERT), involves regular injections of the ADA enzyme to maintain the immune system and can help restore immune function; however, the treatments are extremely expensive and painful for the young patients and the effects are often only temporary.

Given the limitations of HSCT and ERT, in the 1990s researchers began investigating the efficacy of gene therapy for ADA-deficient SCID. They discovered that they could "correct" the function of a mutated gene by adding a healthy copy into the cells of the body that help fight infectious diseases. Since then, there have been significant advances in gene therapy for SCID, yet successful gene therapy in patients with ADA-deficient SCID has been seen in only a small series of children due to the difficulty of introducing a healthy ADA gene into bone marrow stem cells and to engraft these cells back into the patients.

"Although the basic steps of gene therapy for patients with SCID have been known for a while, technical and clinical challenges still exist and we wanted to find an optimized gene therapy protocol to restore immunity for young children with ADA-deficient SCID," said Fabio Candotti, MD, one of the study's senior authors, senior investigator in the Genetics and Molecular Biology Branch of the National Human Genome Research Institute at the National Institutes of Health, and chair of the ASH Scientific Committee on Immunology and Host Defense.

To determine whether an enhanced gene therapy approach would improve immunity in children with ADA-deficient SCID, the teams of Dr. Candotti and Donald B. Kohn, MD, director of the Human Gene Medicine Program at the University of California, Los Angeles (UCLA), Professor of Pediatrics and of Microbiology, Immunology, and Molecular Genetics, and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, conducted a clinical trial in 10 patients with the disorder. For the first time, Drs. Candotti and Kohn and their team of investigators compared two different retroviral vectors, MND-ADA and GCsapM-ADA, to transport normal ADA genes into the young patients' bone marrow stem cells as well as two different treatment plans in preparation for receiving gene therapy. Following therapy, investigators found that more bone marrow stem cells were marked with the MND-ADA vector, demonstrating its superiority over the GCsapM-ADA vector.

The investigators also sought to determine whether providing a low dose of chemotherapy prior to gene therapy, known as a pre-transplant conditioning regimen, would successfully deplete the young patients' bone marrow stem cells and make room for gene-corrected stem cells. In four patients, gene therapy was performed without chemotherapy, and the patients remained on ERT throughout the entire procedure to evaluate the efficiency of ERT combined with gene therapy. While these patients did not experience any adverse effects, they also did not experience a significant increase in their levels of the ADA enzyme. They also maintained low absolute lymphocyte counts (ALC) and minimal immune system function, leading the researchers to believe that ERT may weaken the therapy's effect by diluting the number of gene-corrected lymphocytes.

The remaining six patients were treated with the chemotherapy drug busulfan prior to gene therapy and ERT was discontinued prior to the gene therapy procedure. A significant increase in ADA was observed in all six patients; half of them remain off of ERT with partial immune reconstitution -- findings that support results from prior trials in Italy and the United Kingdom using chemotherapy prior to gene therapy and discontinuting ERT. While the ALC of all six patients declined sharply in the first few months due to combined effects of busulfan administration and ERT withdrawal, their counts increased from six to 24 months, even in the three patients that remained off of ERT. After adjusting the chemotherapy dosage, investigators were able to determine an optimal level for enhancing the efficacy of the gene-therapy-corrected cells with minimal toxicity.

This study is the first to detail comparisons of ADA-deficient SCID patient outcomes between those treated with gene therapy who have not received pre-transplant conditioning while continuing to receive ERT with those receiving pre-transplant conditioning without the administration of ERT. This study is also the first to compare two different viral vectors to transport normal ADA genes into patient bone marrow.

"We were very happy that in this trial we were able to see a benefit in the patients after we modified the protocol," said Dr. Kohn. "Doctors treating ADA-deficient SCID have had too few options for too long, and we hope this will provide them with an efficient and effective treatment for this devastating disease."

Go here to see the original:
Gene therapy technique for children with immune disorder improved

TORONTO, Sept. 10, 2012 /CNW/ - Sigmacon Skin Sciences announced it is the exclusive Canadian distributor of Stemulation, a luxury skin care line that uses the healing power of human stem cells to combat wrinkles and other signs of aging.

Stemulation is based on the science that stem cells can be effectively used for skin rejuvenation, tissue repair and wound healing. A research team of specialists spent two years capturing growth factors from adult human skin cells, which they turned into an active ingredient and the basis for Stemulation products. These growth factors stimulate collagen and the reproduction of new skin cells to reduce wrinkles, eliminate sun spots and smooth scars and fine lines. It truly is a groundbreaking (and technology-backed) new way to achieve younger-looking skin!

The Stemulation line includes a serum, cleanser, exfoliant and face and body creams. The line will be sold through select doctors, estheticians and medical spas.

ABOUT Sigmacon Skin Sciences is the national distributor of a comprehensive set of performance skin care products with dedicated product specialists and trainings all across Canada. Our product lines include professional treatments, sun protection products and results-oriented home care. Sigmacon is also the distributor of advanced medical and aesthetic devices. Visit http://www.skinsciences.ca to learn more.

Image with caption: "The Future of Skin Care: Stemulation Facial Serum and Boost Crme used over 1 year. (CNW Group/Sigmacon Skin Sciences)". Image available at: http://photos.newswire.ca/images/download/20120910_C3135_PHOTO_EN_17420.jpg

The rest is here:
Introducing Canadians to a whole new way to treat aging skin: Stemulation

By Leila B. Salaverria Philippine Daily Inquirer

Former President and now Pampanga Rep. Gloria Macapagal Arroyo: Stem cell treatment

MANILA, PhilippinesLike her predecessor, former President and Pampanga lawmaker Gloria Macapagal Arroyo has turned to stem cell therapy in an effort to improve her health.

Arroyo said in her official Twitter account that she would have her fourth stem cell intravenous treatment with her alternative medicine doctor on Monday.

Arroyo said her treatment would involve cultured stem cells, and it would be much more modest in price than the one coming from sheep or ones own body.

A close friend and ally of Arroyo, Quezon Representative Danilo Suarez, confirmed that the President has started stem cell therapy, and that she told him that the stem cells she has been using did not come from lamb placenta, and was the less costly form of stem cell treatment.

If you have a lot of health problems, you will try such things, Suarez said on Sunday.

Suarez said he has even filed a resolution to investigate the practice of stem cell treatments in the country, as well as the claims being made about it, considering that it has been gaining popularity.

The public needs to be better informed about it. It might have setbacks that we need to know about, he said.

The therapy involves the use of fresh cells, which are injected into the body to regenerate cells to treat illnesses or reverse aging.

See the rest here:
Arroyo undergoes 4th stem cell treatment

Fresh from winning $40 million from the
California stem cell agency, StemCells, Inc., is shooting for
another, $10 million award from the state research effort.

“Already looking ahead, StemCells has
set its sights on one more CIRM initiative designed to fund early
stage clinical trials over a four-year period. StemCells has applied
for that grant, worth up to $10 million, to fund a Phase II trial in
PMD(Pelizaeus-Merzbacher disease).”

"We're the only company that has
programs going on in all three regions of the central nervous system:
the brain, the spinal cord and the eye."

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Frustrated with politicking,
“arm-twisting,” lobbying and “emotionally charged
presentations,” the governing board of the $3 billion California
stem cell agency today approved short-term changes in its grant
appeal process and ordered up a study to prepare long-term reforms.

"I don't think we can run a board
this way. If we do, it would be chaos." 

“On big money grants, people will be
calling their friends.”

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Directors of the California stem cell agency today approved about $38 million for research into basic biology, including two appeals by researchers on applications initially rejected by reviewers.

The governing board turned down five appeals in the round, which attracted 357 applications in its "pre-app" process, 64 of which were invited to apply. Reviewers approved 25 applications.

The following appeals in the biology round were approved:

• $1.3 million, Deborah Lieu of UC Davis. (Review summary here, appeal here.) 764
• $1.4 million, Yanhong Shi  of the City of Hope. (See review summary here and appeal here.)

The board also approved another application that was rejected by reviewers based on a recommendation by CIRM President Alan Trounson.  It is very unusual for the board to approve rejected applications based on staff recommendations following a review. Trounson described the grant addressed a major bottleneck in stem cell science.

 The California stem cell agency is expected to post a press release shortly with the names of all recipients. The agency usually withholds names of applicants until the the board formally acts.
(An earlier version of this item reported that the board approved $37 million in grants.)

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Dennis Steindler UF Photo

The governing board of the California stem cell agency this morning approved a $6.7 million grant to recruit Dennis Steindler of the University of Florida to the Parkinson's Institute in Sunnyvale, Ca.

The grant was approved immediately following a 45-minute executive session with no further debate. (For more on this, see here, here and here.)

Steindler later told the California Stem Cell Report he would begin work in California as soon as possible.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

The governing board of the California stem cell agency has just concluded a 45 minute executive session on a $6.7 million grant to recruit a Florida scientist to the Parkinson's Institute in Sunnyvale, Ca.

It was the longest executive session ever on a recruitment grant, which are usually approved routinely with little serious discussion.

The board is now resuming discussion of the matter(see here and here.)

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

"In summary, this is an
application from an established leader in NSC biology to pursue
research focused on disease mechanisms in PD. Strengths of the
proposal include the quality of the PI, the focus of the project on
an interesting hypothesis, and the leadership in basic science that
the candidate would bring to the applicant institution. Weaknesses
included deficiencies in the research plan, the limited track-record
of the PI in PD research and an institutional environment lacking
adequate support for basic science investigations."

"During programmatic discussion some GWG (grant review group) members cited a need to broaden stem cell leadership not only at the
large universities but also at the smaller institutions as well. They
felt that the candidate's recruitment would strengthen the applicant
institution and provide leadership and strength in basic research.
The need for increased research focused on Parkinson's Disease was
also cited by some reviewers. A motion to recommend the application
for funding carried with a majority vote. Because more than 35% of
GWG members opposed the motion, opponents have exercised their right
to have that position reported to the ICOC. The consensus statement
from this group is as follows: 'Despite the facts that the
applicant has many excellent attributes, that Parkinson's disease is
a key area of interest, and that the applicant institution may
deserve additional consideration, our opinion is that the application
clearly falls short in several critical scientific areas that
outweigh the programmatic concerns and do not justify a
recommendation for funding. We believe that the people of California
depend upon us to make recommendations based on our scientific
expertise, for outcomes that are most likely to impact medicine and
the health and treatment of their citizens. We believe that their
money can be better spent.'"

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

The board of the California stem cell agency is discussing a proposal to award $6.7 million to recruit a Florida scientist to the Parkinson's Institute in Sunnyvale, Ca.

The scientist is Dennis Steindler of the University of Florida. The recruitment award received a score of 57, although the scores ranged from 30 to 75.  Jeff Sheehy, a member of the grant review group and CIRM board member, said the score reflected two extremely divergent positions by two reviewers.

The board has awarded four grants in its recruitment round over the past couple of years, but this is the first extended discussion of an award recommended by reviewers. It is also the first to have a representative of the applicant institution speaking publicly for the grant.

CIRM directors have now moved into executive session to discuss matters they prefer to air in private.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

The governing board of the California stem cell agency last night rejected appeals by two applicants -- OncoMed Pharmaceuticals of Redwood City and Albert Wong of Stanford -- in the $200 million disease team round.

Both petitions generated little discussion. You can find more on their petitions here and here.

The board also approved changes in its intellectual property and grant administration rules. Both proposals will now enter the state's official administrative law process for more comment and possible change.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

StemCells, Inc., was quick this morning
with a press release about winning a $20 million award last night from the
California stem cell agency.

 "CIRM's approval of two
awards to StemCells illustrates the tremendous promise of
our neural stem cell technology and the high degree of confidence in
the world class team of scientists and clinicians who will be working
to translate this technology into potential treatments and cures for
these devastating diseases." 

 "With the recent spate of late-stage clinical
failures in Alzheimer's disease, it is clear that the field could
benefit from alternative approaches to lessen the huge burden on
families, caregivers and our healthcare system.

"Our recently reported preclinical
data, which showed that our neural stem cells restored memory and
enhanced synaptic function in two animal models relevant to
Alzheimer's disease, shows our approach has promise. We greatly
appreciate the support from CIRM, which should help us accelerate our
efforts to test our HuCNS-SC cells in Alzheimer's disease."

 “We are reiterating our strong
speculative buy with a price target of $4.50 as StemCells Inc.
continues to distinguishing themselves as one of the most advanced
players in the stem cell space.”

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Following a second impassioned pitch by its former chairman, Robert Klein, the governing board of the California stem cell agency approved a $20 million award to a financially strapped biotech firm, StemCells, Inc., of Newark, Ca.

Approval came on a 7-5 vote with the condition that the company demonstrate it has access to $20 million in matching funds prior to funding.  It is the second $20 million award that the company has received in the disease team round, which now totals $214 million. Another disease team application has been tabled and will not be considered until October.

The current CIRM chairman, J.T. Thomas, a Los Angeles bond financier, asked for the financial proof because he said some concerns were expressed during an executive session that CIRM would now "account for such a large part of the assets of the company." Martin McGlynn, CEO of StemCells, Inc., also told the board that the company might have to drop its Alzheimer's research if it did not receive the CIRM award.

The StemCells, Inc., application was rejected twice by reviewers. The original rejection came before the July meeting at which Klein first appeared (see here and here). The proposal was then sent back for re-review, during which it was rejected again.

However, the 29-member board narrowly approved the application following discussion tonight and following its rejection of another Alzheimer's research proposal from USC. Both applicants produced a number of witnesses, including patients, on behalf of their appeals.

“The reviewers did not feel there was compelling data for neuron migration in the submitted manuscript. This is the manuscript specifically referenced at the ICOC (CIRM governing board) meeting (in July) that prompted the call for additional analysis. The manuscript is not yet accepted, it is 'potentially acceptable' but requires 'major revisions' according to the journal editor note. In addition, however, the studies in this manuscript used mouse NSCs, not the human NSCs proposed for the disease team award....”

A footnote: The CIRM staff said that as a result of two StemCells application, a proposal is being prepared to limit applications to one per entity in later rounds.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Researchers have discovered a cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, according to a release from the University of California, Los Angeles. This finding promises to lead to a more profound understanding of how a healthy immune system is created and as well as how disease can cause poor immune function.

The study's senior author, Dr. Gay Crooks, was quoted as saying, " We felt it was especially important to do these studies using human bone marrow, as most research into the development of the immune system has used mouse bone marrow.The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of post-natal life."

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, cancers of the blood. The findings were published online in the journal Nature Immunology.

"The identification of a progenitor in human bone marrow primed for full lymphoid differentiation will now permit delineation of the molecular regulation of the first stages of lymphoid commitment in human hematopoiesis," the authors wrote. "It will also allow understanding of how these processes are affected during aberrant hematopoiesis in disease states."

Continued here:
Stem Cells & Immune System: "Missing Link" Found

NEW YORK, Sept. 5, 2012 (GLOBE NEWSWIRE) -- NeoStem, Inc. (NBS) ("NeoStem" or the "Company"), a cell therapy company, today announced that Company management of a NeoStem company, Progenitor Cell Therapy ("PCT"), an internationally recognized contract development and manufacturing organization (CDMO), has been invited to present on its core expertise in development of commercial manufacturing processes for cell therapy at two cell therapy conferences in September. At each, PCT will offer its unique perspective as an industry leader in contract development and manufacturing of cell therapy products, with over 12 years of exclusive cell-therapy focused experience.

Timothy Fong, Ph.D, M.B.A, PCT's Vice President, Technology and Product Development, will be sharing PCT's expertise in cell therapy manufacturing with a focus on commercialization. At IBC Life Sciences' Cell Therapy Bioprocessing Conference, he will chair a panel on quality assurance and controls and will give a presentation entitled "From Concept to Product: Considerations for Developing a Robust Commercial Manufacturing Process", which will include considerations for developing a robust commercial manufacturing process. He will also speak at the Stem Cells USA and Regenerative Medicine Congress on "Cell manufacturing considerations for first-in-world stem cell therapeutics".

Dr. Fong stated, "As a cell therapeutic progresses from concept to product, the development of a commercial manufacturing process may contain unexpected technical and quality issues. The development path should follow several defined steps. My presentations will discuss the key steps in the process and highlight critical areas that need to be addressed to develop a successful commercial manufacturing process. PCT helps clients bridge the gap between discovery and patient care through efficient transfer of cell-based therapies from laboratory into clinical practice."

NeoStem and PCT invite you to attend the conference(s), see Dr. Fong's talks, and connect with the PCT team at PCT's booths. If you are a colleague of PCT or NeoStem, PCT can offer you a registration discount. Please contact PCT at bdm@pctcelltherapy.com for more details.

IBC Life Sciences' 2nd Annual Cell Therapy Bioprocessing Conference

Terrapinn 4th Annual Stem Cells USA and Regenerative Medicine Congress

About NeoStem, Inc.

NeoStem, Inc. continues to develop and build on its core capabilities in cell therapy capitalizing on the paradigm shift that we see occurring in medicine. In particular, we anticipate that cell therapy will have a large role in the fight against chronic disease and in lessening the economic burden that these diseases pose to modern society. We are emerging as a technology and market leading company in this fast developing cell therapy market. Our multi-faceted business strategy combines a state-of-the-art contract development and manufacturing subsidiary, Progenitor Cell Therapy, LLC ("PCT") with a medically important cell therapy product development program, enabling near and long-term revenue growth opportunities. We believe this expertise and existing research capabilities and collaborations will enable us to achieve our mission of becoming a premier cell therapy company.

Our contract development and manufacturing service business supports the development of proprietary cell therapy products. NeoStem's most clinically advanced therapeutic, AMR-001, is being developed at Amorcyte, LLC ("Amorcyte"), which we acquired in October 2011. Amorcyte is developing a cell therapy for the treatment of cardiovascular disease and is enrolling patients in a Phase 2 trial to investigate AMR-001's efficacy in preserving heart function after a heart attack. Athelos Corporation ("Athelos"), which is approximately 80%-owned by our subsidiary, PCT, is collaborating with Becton-Dickinson in the early clinical exploration of a T-cell therapy for autoimmune conditions. In addition, pre-clinical assets include our VSELTM Technology platform as well as our mesenchymal stem cells product candidate for regenerative medicine. Our service business and pipeline of proprietary cell therapy products work in concert, giving us a competitive advantage that we believe is unique to the biotechnology and pharmaceutical industries. Supported by an experienced scientific and business management team and a patent and patent pending (IP) portfolio, we believe we are well positioned to succeed.

For more information on NeoStem, please visit http://www.neostem.com. For more information on PCT, please visit http://www.pctcelltherapy.com.

Originally posted here:
Progenitor Cell Therapy, a NeoStem Company, Invited to Present at Two Conferences in September

Forbes

Genetic Engineering: A Food Fix? Forbes Genetic engineering, in the short term, then would save us the pollution, expense and growing weed resistance caused by pesticides. But in the long term, these weeds (and perhaps the insects as well) will also become resistant to the genetically ...

Source:
http://news.google.com/news?q=genetic-engineering&output=rss

KAALtv.com

Elk Run Biotechnology Center is a Slow Process KAALtv.com (ABC 6 News) -- It's a project years in the making, but many are now wondering what is going on with the Biotechnology Center in Pine Island. It's a sign that carries much more than a name of a yet to be developed technology campus. Promises of high ...

Source:
http://news.google.com/news?q=biotechnology&output=rss

Cell therapies present unique challenges when complying with this paradigm for several reasons only two of which I will mention here.  Firstly, it is not possible to achieve the level of product purification as one might with other therapeutic products.  Secondly, the product characterization is at a cellular rather than molecular level.

Autologous cell therapies present another set of unique challenge in this paradigm because of the notable patient-to-patient variability where the patient is also the donor of the raw material.  This often means there is a wider tolerance of heterogeneity in the product but it still must be within what has been proven to the regulatory agency as a safe and effective range.  


In cases where an autologous cell therapy is centrally manufactured, they are most often subjected to product release testing similar to that described above.  One notable difference, particularly for fresh products, is that the products may be shipped to the clinic and even administered before the full panel of test results are obtained.  This wold be considered highly unusual (if ever acceptable) with other types of products but is tolerated because of the time-sensitivity of these products and their high safety profile.


In the case of autologous cell therapy products produced at the bedside there is often not the same kind of product release discipline.  Often the regulatory agencies deal with the product consistency and specification compliance issue by ensuring that the cell processing device used point-of-care is validated to ensure the cellular product output is always within a specified range shown to be clinically safe and effective.


The Varying Degree of Product Characterization/Specification of Autologous GTP Cell Therapy Products


However - and now I get to the point of this blog post - for cell-based products, procedures and/or devices/kits which are not mandated to be formally approved by a regulatory agency before they can be commercially marketed, there is no product specification rigor.  Compliance with the Good Tissue Practice regulations and guidance is deemed to ensure safety.  In the United States, cell-based products which are deemed to be "minimally manipulated" and intended for "homologous use" are typically allowed to go straight to market with no formal approval.  Safety and clinical data is not required but is practically necessary to support physician adoption and, where applicable, reimbursement.  


This means that for these products there is a great deal of variability in terms of how much rigor companies apply in characterizing their product and then ensuring that each batch complies with the specifications they themselves have determined to be safe and effective. Again, where such products are manufactured in a centralized facility the likelihood of some release testing is greater.  However, those companies relying on a point-of-care processing kit or device business model that has not been deemed to require formal market approval, rarely (if ever) include product release testing.


The common criticism of these companies is that they simply do not know what they are injecting into patients because of the combination of the patient-to-patient donor variability, the lack of any disciplined product characterization or dosing studies, and the absence of any product release testing.  


This criticism is not equally levied at all autologous GTP products or companies - even those relying on point-of-care processing.  Of course some companies care and do a lot to try to ensure their product is well-characterized and that each batch complies with product specifications. This may involve the use of product release tests but can also involve the combination of pre-market research into the product characterization, safety, and dosing along with validation of the device/kit output.  In this way a company can say that within a very small margin, the output will be within the product specifications the company knows is safe and efficacious.


However, in a rush to get their device/kit to market some companies appear to care very little about the cell product characterization, validation of the output of their device/kit, or tying this data to optimal dose.


More concerning are those companies that appear to provide such data but it is wrong or meaningless.  What follows appears to potentially be a case study of precisely this problem. 


The INCELL Study 


This week I came across a fascinating white paper from Incell Corporation analyzing the output of adipose tissue processing kits of MediVet-America apparently demonstrating the inaccuracy of their cell counts (a common type of cell therapy product characterization) and calling into the question the cell count claims of Intellicell Biosciences (New York, NY) and Adistem (Hong Kong).


At the heart of the critique is the claim that the cell counting (product characterization) techniques employed by these companies counts as cells things (namely acellular micelles) which are not cells.

I encourage you to read the white paper in its entirety.  They corresponding author told me to watch for one or more papers which they are preparing for submission to peer-reviewed publications shortly.  Presumably these will rely on a larger data set and perhaps test other methodologies or technologies.


For the purposes of this blog, I've pulled what I believe are the most salient excerpts below:

Intrigued by the high cell numbers  (5 to 20 million cells/gram)  reported by kit/device manufacturers such as MediVet-America (Lexington, KY), Intellicell  Biosciences (New York, NY), and Adistem, Ltd. (Hong Kong) in adipose stem cell therapy compared to other methods (e.g., 
Chung,Vidal, and Yoshimura), INCELL staff conducted a research study to  investigate the high apparent yield of stem cells.  This initial work was focused  on SVF cells from the MediVet Kit, which is marketed to isolate adiposederived canine SVF and stem cells.

The cell yields reported for the Medivet Kits are five to more than ten times higher than the yields routinely obtained by INCELL from freshly harvested human or animal adipose tissue using our adipose tissue processing methods.  These yields are also tenfold or higher than those reported in the literature by most academic researchers (Chung-canine, Vidal–equine, Yoshimura–human).  Since these  cell counts are used to support stem cell dosing recommendations and cell banking, it is important to better understand why the cell numbers are higher.

...

A comparative analytical study of three dog donors of adipose tissue was designed to evaluate the cell yields using the MediVet Kit as an example of this class of isolation system. All  kit procedures were followed as per the instructions provided.  A brief overview of the different cell counting methods used, and the resultant cell counts, observations and explanations of the results observed, are described below

....

This study shows that incorrect counting of adipose derived SVF cells and the subset of regenerative stem cells can subsequently result in inaccurate dosing, both in direct therapeutic applications and in cryostorage of cells for future use.  The DAPI-hemocytometer cell count (manual) was considered the most accurate, but there are various sources of technical difficulties that  can lead to incorrect  cell numbers. The nature of adipose tissue itself with variability in dissociation by enzymatic digestion can all contribute to the outcomes. Fat tissue has a propensity to form acellular micelles and oils upon tissue disruption. Processing methods or reagents (e.g., Solution E or lecithins) can generate micelles that may be  erroneously  counted as cells. Autofluorescence and dye trapping or uptake by the micelles can lead to very high inaccurate cell counts when automated cell counting is used. 

In this study the most inaccurate counting came from the Cellometer. When used according to kitrecommended guidelines and on-site training provided by Nexelcom for counting  cells by the MediVet procedure, the Cellometer overstated the DAPI-hemocytometer cell count by up to 20X or more. The Coulter Counter protocols also led to incorrect, high cell numbers. Although the cell counts were still a bit high, the authors recommend the NucleoCounter, or similar equipment, as more acceptable for automated counting.  The manual hemocytometer-DAPI method is the most accurate, but requires a highly experienced cell biologist or technician to make accurate counts and  is not suitable for routine clinical use. 

...

Other companies also have claims of very high cell numbers when their processes are used. Adistem, like MediVet, states they add an emulsifying agent to their kits to assist in cell release, and they also use a light activation system. Their kits were not tested in this study but it is possible that the high cell numbers reported by Adistem are also incorrect and result from the same problems highlighted in this paper for the MediVet procedure. Ultrasonic energy, which is commonly used to manufacture micellular  liposome  structures and to disrupt and lyse cells, is  another potentially problematic procedure for counting and verifying viable, regenerative cells.  Intellicell 3uses ultrasonic energy to release cells from adipose tissue, and it is possible that resultant micelles or cell fragments contribute to the higher than expected cell numbers.  This assumption could be verified with additional studies.  

In summary, the authors caution that great care must be taken when using kits and automated cell counting for stem cell dosing and cryobanking of cells intended for clinical use. Overestimated  cell numbers would be a major confounding source of variation when efficacy of stem cells injected are compared as doses based on cell number and when cryostored cells are aliquoted for use based on 

specific cell numbers as a treatment dose.  Hopefully, this study will lead to more  reproducible counting and processing methods being reported in the literature, more inter-study comparability of cell doses to clinical outcomes,  more industry diligence to support claims, and more accurate counting for dosing stem cell therapies to patients.

...

Chung D, Hayashi K, Toupadakis A, et al.  Osteogenic proliferation and differentiation of canine bone marrow and adipose tissue derived mesenchymal stromal cells and the influence of hypoxia.  Res Vet Sci, 2010; 92(1):66-75. Vidal MA, Kilroy GE, Lopez MJ, Johnson JR, Moore RM, Gimble JM. Characterization of equine adipose tissue-derived stromal cells: adipogenic and osteogenic capacity and comparison with bone marrow-derived mesenchymal stromal cells. Vet Surg, 2007; 36:613–622.  Yoshimura K, Shigeura T, Matsumoto D, et al:  Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirate.  J Cell Phys, 2006; 205:64-76.

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The chairs are shifting a tad on the
governing board of the $3 billion California stem cell agency as a
French immigrant is added, a Latino leaves and a veteran patient
advocate is reappointed.

Anne-Marie Duliege Affymax Photo

State Controller John Chiang appointed
Duliege to the CIRM post, saying, 

“Dr. Duliege brings
first-hand knowledge of what is required to take a drug from research
phase through FDA approval.”

David Serrano Sewell CIRM Photo

Serrano Sewell, who has also served on
the CIRM board since its inception, is apparently resigning to accept
an appointment to the board that regulates
California physicians. Apparently – because the stem cell agency
has not confirmed that he is leaving, although this morning it placed a resolution honoring him on the agenda for next week's meeting.  That almost invariably means a board member is departing.

Jeff Sheehy CIRM Photo

Sheehy was reappointed recently by
state Senate President Pro Tem Darrell Steinberg. Sheehy is a
communications manager at UC San Francisco and a nationally known
HIV/AIDS advocate. He is co-chairman of CIRM's Science Subcommittee
and vice chairman of the grants review group. Sheehy leads the
discussion of grant applications when they come before the full board
in public session.

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A robust discussion has arisen
concerning Bob Klein and his appearance last month before the
governing board of the $3 billion California stem cell agency, a body
that he once chaired and an enterprise that he once oversaw.

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