StemCell Therapy

This morning, StemCells, Inc. (STEM) released six-month interim results for the first group of patients in its Phase I/II trial, testing the company`s HuCNS-SC (human neural stem cells) treatment candidate in patients with spinal cord injury - previous coverage available here. Shares are trading up nearly 20% in pre-market, and are likely to maintain momentum on the positive news. The interim data showed that thus far, HuCNS-SC treatment led to considerable gains in sensory function in two of three patients vs. their baseline levels of sensation prior to cell transplantation. The company also noted that the treatment continues to exhibit a favorable safety profile. The trial represents the first time that neural stem cells have been transplanted as a potential therapeutic agent for spinal cord injury, and the sensory gains observed have developed in a progressive pattern below the level of injury. Impressively, gains in sensation are not generally expected in spinal cord injury patients, particularly given the severity of injury seen in patients admitted to the Phase I/II study. According to STEM, sensory function of all patients observed thus far was stable before cell transplantation, therefore, the reappearance of sensation is a very positive sign that the treatment is having a beneficial effect. While the third patient did not experience an increase in sensation, that patient`s level of sensation remains stable. PropThink notes that another small-cap stem cell company, PluriStem Therapeutics (PSTI) is also moving in pre-market trading, likely in sympathy with the STEM news.

To see this article at PropThink.com, click here.

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PropThink: Interim Data In Spinal Cord Injury Driving STEM Higher; PSTI Reacting in Sympathy

CLEVELAND, Ohio -- One of the most promising and exciting treatment avenues for multiple sclerosis is the use of a patient's own stem cells to try to stop -- or even repair -- some of the disease's brain tissue damage.

But injecting a patient with a dose of his or her own bone-marrow stem cells was actually a pretty crude method of treating the disease, because no one was quite sure how or why it worked. Last year, doctors at the Cleveland Clinic, University Hospitals Seidman Cancer Center and Case Western Reserve University began trying this for MS patients in a Phase 1 clinical trial after positive results were seen in mice.

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.

Like many other researchers using stem cells, the local group didn't know exactly how their treatment worked, but they knew that when they gave these human mesenchymal stem cells, or MSCs, to mice with a mouse version of the disease, the mice got better.

Figuring out why the mice improved could help researchers see if the MSC injection will work well in a particular patient before the patient is injected, and possibly augment or improve the treatment as well.

In May, the research group at CWRU, headed up by neurosciences professor Robert Miller, discovered exactly what it is in the stem-cell soup that has a healing effect: a large molecule called hepatocyte growth factor, or HGF. The team published their results in Nature Neuroscience.

Miller's group knew that it could be the stem cells themselves, by coming in physical contact with the myelin damage, that were having a healing effect. Or it could be something the stem cells secreted into the surrounding liquid culture, or media, they were grown in, that was key. HGF is secreted by the stem cells, Miller said.

The team identified the HGF by first injecting only the liquid the stem cells were grown in, but not the stem cells themselves, into the mice they were studying. The mice got better, so the team knew whatever was helping was in the media.

Next, they isolated the small, medium and large molecules from the media and tried each size on the mice. Only the large-molecule treatment had the healing effect, meaning that whatever was helping was somewhere in that mix, Miller said.

"The molecule that jumped out at us was HGF," he said, because it is the right size, is made by MSCs, and in a couple of studies had been shown to be involved in myelin repair.

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Cleveland researchers find key to stem-cell therapy for MS patients: Discoveries

- Safe and Effective Results from Adipose Derived Adult Stem Cells manufactured by RNL BIO

SEOUL, South Korea, Sept. 4, 2012 /PRNewswire/ -- Korean researchers, reporting the results of a major study in the Circulation Journal, found that the transplantation adipose (fat) derived stem cells resulted in the regeneration of blood vessels in patients who were otherwise expecting to receive limb amputations due to damaged arteries and lack of blood circulation.

Researchers at Pusan National University, led by Dr. Han Cheol Lee, describe how patients with critical limb ischemia (hereafter, CLI, example of which include Buergers Disease and diabetic foot ulcers) were injected with adipose tissue-derived mesenchymal stem cell manufactured by RNL BIO.

As a result of the remarkable adipose stem cell process of RNL BIO, researchers found that immediate new blood vessel generation was identified. (The title of article is "Safety and Effect of Adipose Tissue-Derived Stem Cell Implantation in Patients With Critical Limb Ischemia")

CLI results from lack of circulation due to small artery damage and subsequent tissue necrosis. Patients with severe CLI often face limb amputation. Buergers Disease, or diabetic foot ulcer, are of the same kind. Risk factors are diabetic mellitus, hypertension, high cholesterol and smoking. There is no known cure to date.

Currently percutaneous transluminal angioplasty or PTA may treat 60-70% of patients with CLI, but it doesnt work with those who suffer from Buergers Disease. Working under approval to conduct compassionate use research of stem cell to treat CLI by intra-muscular injection of adipose tissue derived stem cells in December, 2008 (KFDA IND approval # 1273), the researchers in this study enrolled 15 subjects: 12 with Buergers Disease, and 3 with Diabetic foot ulcers. 300 million stem cells were injected into each patients leg. No complications were observed, even six months after injection.

Only five patients, as they all had expected, required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted in pain and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries.

Dr. Jeong-Chan Ra, President of RNL Stem Cell Technology Institute, said, "This new therapy through adipose tissue derived mesenchymal stem cell is expected to offer new hope for patients with CLI, hope that had been difficult to find before."

RNL Stem Cell Technology Institute

Original post:
First Evidence that Adipose Stem Cell-Based Critical Limb Ischemia Treatment is Safe & Effective is published in ...

NEW YORK (CBSNewYork) - Cases of autism have soared in recent years: one in every 88 children is diagnosed with the disorder. Now, a groundbreaking clinical trial will test whether a childs own stem cells the building blocks of the body might help.

Dr. Michael Chez of the Sutter Neuroscience Institute wants to look at the relationship between the immune system and the central nervous system, and it is his hope that he will be able to use stem cells to help behavioral and developmental issues in autistic children.

Elisa Rudgers son, Rydr, was diagnosed with cerebral palsy at 11 months, he couldnt sit up on his own and required feeding tubes to eat. At 15 months, doctors gave Rydr his first infusion of banked cord blood stem cells that his parents saved while he was a newborn. His developmental delays diminished quickly.

After the first infusion after three months, he was crawling, six months he was standing, and nine months he was walking. said Rudgers.

Rudgers said that her 4-year-old son likes the spotlight because hes become something of a medical marvel. Hes gotten lots of attention.

Rydrs stem cells apparently helped at least partly rebuild his damaged brain. Now, Rydrs doctor is enrolling patients in a clinical trial to see if the same treatment thats helped this little boy, can help treat autism. Dr. Chez believes it can.

Theres enough encouraging evidence to think there may have a role to play here, but were opening a new door and thats the giant step. he said.

Can Rydrs reversal be repeated?

Many experts are skeptical, saying its unclear what or where the brain defect in autism actually is. Dr. Chez says stem cells could regenerate missing brain cells or help repair faulty connections between brain cells.

Either way, Ryders mom says, its worth a try.

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Clinical Trial With Stem Cells Creates Hope For Parents Of Autistic Children

MARLBOROUGH, Mass.--(BUSINESS WIRE)--

Advanced Cell Technology, Inc. (ACT; OTCBB: ACTC), a leader in the field of regenerative medicine, announced today that its chief scientific officer, Robert Lanza, M.D., will be delivering the opening Keynote Speech at the 4th Annual Stem Cell Symposium 2012, being held in Singapore, September 6-7. Dr. Lanzas presentation is titled Pluripotent Stem Cells From Benchtop to Clinic.

With the theme, Stem Cell Based Therapy, the symposium will have a particular focus on clinical trials and industrial application of stem cells. Sponsored by Stem Cell Society of Singapore (SCSS), the conference will include scientific presentations from key contributors from academic, clinical, and commercial organizations who are translating basic research on stem cells into therapeutics, with a focus on applying engineering technologies to provide medical solutions.

In their opening statement, the organizers state, We are all keeping our fingers crossed for ACTs success, which will also bring a big boost to the stem cell community.

Other topics of the conference include human induced pluripotent stem cells (hiPSCs), drug screening, adult and cancer stem cells, and stem cell therapies emerging from Asia, with presentations from Indian, Korean and Japanese regenerative medicine companies. There will also be a joint session with the International Society for Cellular Therapy (ISCT) covering important issues concerning the commercialization of stem cells, and addressing issues such as reimbursement, manufacturing, characterization, and clinical implementation issues unique to cell therapies.

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc. is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visit http://www.advancedcell.com.

Forward-Looking Statements

Statements in this news release regarding future financial and operating results, future growth in research and development programs, potential applications of our technology, opportunities for the company and any other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including statements containing the words will, believes, plans, anticipates, expects, estimates, and similar expressions) should also be considered to be forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by such forward-looking statements, including: limited operating history, need for future capital, risks inherent in the development and commercialization of potential products, protection of our intellectual property, and economic conditions generally. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in the companys periodic reports, including the report on Form 10-K for the year ended December 31, 2011. Forward-looking statements are based on the beliefs, opinions, and expectations of the companys management at the time they are made, and the company does not assume any obligation to update its forward-looking statements if those beliefs, opinions, expectations, or other circumstances should change. Forward-looking statements are based on the beliefs, opinions, and expectations of the companys management at the time they are made, and the company does not assume any obligation to update its forward-looking statements if those beliefs, opinions, expectations, or other circumstances should change. There can be no assurance that the Companys clinical trials will be successful.

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ACT’s Chief Scientific Officer Dr. Robert Lanza to Deliver Opening Keynote Address at 4th Annual Stem Cell Symposium ...

GAITHERSBURG, MD--(Marketwire -09/04/12)- Cytomedix, Inc. (CMXI) (CMXI), a fully integrated regenerative medicine company commercializing and developing innovative platelet and adult stem cell technologies, today announced that the Company's AutoloGel System was highlighted in a continuing education program at the Paralyzed Veterans of America Summit 2012 held August 28 to 30 at the Paris Las Vegas Hotel.

The AutoloGel System is a device for the production of autologous platelet rich plasma ("PRP") gel, and is the only PRP device cleared by the U.S. Food and Drug Administration ("FDA") for use in wound management.

The program, titled, "Platelet Rich Plasma (PRP) Gel for Wounds on Persons with SCI," was delivered by Laurie Rappl, PT, DPT, CWS, Clinical Development Liaison for Cytomedix. Ms. Rappl's discussion addressed the underlying mechanisms of action that allow the Company's physiologically relevant concentration of PRP in the AutoloGel System to accelerate healing in recalcitrant wounds in patients with Spinal Cord Injuries ("SCI"), and highlighted the clinical data demonstrating rapid reduction in wound area and volume, as well as reduction of undermining and sinus tracts/tunnels in non-healing wounds in patients with SCI.

"The physiology of SCI -- such as decreased blood flow, blood pressure and blood supply -- causes impairment at every step of the wound healing process. A physiologically relevant concentration of PRP has been shown to improve healing in even the hardest to treat chronic wounds in SCI patients," noted Ms. Rappl.

"It is especially rewarding for Cytomedix to have a continuing education program highlighting the benefits of the AutoloGel System for the treatment of chronic wounds in SCI patients. Pressure ulcers and other chronic wounds are persistent medical challenges that compromise the health and quality-of-life for these paralyzed patients," stated Martin P. Rosendale, Chief Executive Officer of Cytomedix. "Our clinical data demonstrates how the AutoloGel System's physiologically relevant concentration of PRP can rapidly restart the healing process in complex and chronic wounds, including wounds that were recalcitrant to other treatments."

About The Paralyzed Veterans of America SummitParalyzed Veterans' Summit 2012 + EXPO brings together more than 700 healthcare professionals in SCI and multiple sclerosis (MS) care. Doctors, nurses, occupational therapists, physical therapist, social workers and researchers convene to explore and implement holistic strategies to strengthen the continuum of care for SCI and MS patients.

The Paralyzed Veterans of America Summit serves as an educational venue bringing together professionals representing the full spectrum of SCI and MS healthcare and to support clinicians in their pursuit of maintaining their specialty certification and/or license to practice. The objectives are to enhance multi-specialty care across the lifespan of individuals with SCI and MS; to assess advances in the delivery of healthcare services; to present innovative models of care management; to improve practice skills of clinicians, surgeons, researchers and administrators; to discuss evidence-based medicine; to increase the body of knowledge on spinal cord injury and multiple sclerosis, their medical complications and consequences; to promote educational opportunities; to identify research priorities; and to present data on new developments in assessment and treatment.

About Cytomedix, Inc. Cytomedix, Inc. is a fully integrated regenerative medicine company commercializing and developing innovative platelet and adult stem cell separation products that enhance the body's natural healing processes. The Company's advanced autologous technologies offer clinicians a new treatment paradigm for wound and tissue repair. The Company's patient-derived PRP systems are marketed by Cytomedix in the U.S. and distributed internationally. Our commercial products include the AutoloGel System, cleared by the FDA for wound care and the Angel Whole Blood Separation System. The Company is developing novel regenerative therapies using our proprietary ALDH Bright Cell ("ALDHbr") technology to isolate a unique, biologically active population of a patient's own stem cells. A Phase 2 trial evaluating the use of ALDHbr for the treatment of ischemic stroke is underway. For additional information please visit http://www.cytomedix.com.

Safe Harbor StatementStatements contained in this press release not relating to historical facts are forward-looking statements that are intended to fall within the safe harbor rule for such statements under the Private Securities Litigation Reform Act of 1995. The information contained in the forward-looking statements is inherently uncertain, and Cytomedix' actual results may differ materially due to a number of factors, many of which are beyond Cytomedix' ability to predict or control, including among many others, risks and uncertainties related to the Company's reimbursement related efforts, the Company's ability to capitalize on the benefits of the above-referenced CMS determination, the Company's ability to successfully and favorably conclude the negotiations and related discussions with the above-referenced global pharmaceutical company, the Company's ability to successfully integrate the Aldagen acquisition, to successfully manage contemplated clinical trials, to manage and address the capital needs, human resource, management, compliance and other challenges of a larger, more complex and integrated business enterprise, viability and effectiveness of the Company's sales approach and overall marketing strategies, commercial success or acceptance by the medical community, competitive responses, the Company's ability to raise additional capital and to continue as a going concern, and Cytomedix's ability to execute on its strategy to market the AutoloGel System as contemplated. To the extent that any statements made here are not historical, these statements are essentially forward-looking. The Company uses words and phrases such as "believes", "forecasted," "projects," "is expected," "remain confident," "will" and/or similar expressions to identify forward-looking statements in this press release. Undue reliance should not be placed on forward-looking information. These forward-looking statements are subject to known and unknown risks and uncertainties that could cause actual events to differ from the forward-looking statements. More information about some of these risks and uncertainties may be found in the reports filed with the Securities and Exchange Commission by Cytomedix, Inc. Cytomedix operates in a highly competitive and rapidly changing business and regulatory environment, thus new or unforeseen risks may arise. Accordingly, investors should not place any reliance on forward-looking statements as a prediction of actual results. Except as is expressly required by the federal securities laws, Cytomedix undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, changed circumstances or future events or for any other reason. Additional risks that could affect our future operating results are more fully described in our U.S. Securities and Exchange Commission filings, including our Annual Report on Form 10-K for the year ended December 31, 2011 and other subsequent filings. These filings are available at http://www.sec.gov.

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Cytomedix's AutoloGel System Featured in Continuing Education Program at the Paralyzed Veterans of America Summit 2012

BURLINGTON, Mass.--(BUSINESS WIRE)--

AlloCure, Inc. today announced that it has initiated a phase 2 clinical trial of AC607, the companys mesenchymal stem cell therapy, as a potential treatment for acute kidney injury (AKI). The randomized, double-blind, placebo-controlled, multi-center trial, designated ACT-AKI (AC607 Trial in Acute Kidney Injury) (NCT01602328), will enroll 200 cardiac surgery subjects at leading tertiary care centers in the United States.

ACT-AKI follows the positive results from a phase 1 AC607 trial in cardiac surgery subjects, which showed an excellent safety profile and encouraging data on the incidence of AKI and hospital length of stay, said Robert M. Brenner, M.D., AlloCure President and Chief Executive Officer. We have worked closely with leaders in the field on the design of ACT-AKI, and trial initiation represents an important milestone for AlloCure and the patients we collectively serve.

AC607 is a promising therapeutic candidate for AKI, for which effective therapies are greatly needed, said Richard J. Glassock, M.D., Emeritus Professor of Medicine at the Geffen School of Medicine at the University of California, Los Angeles. The initiation of ACT-AKI represents a critical step in the development of an innovative therapy for this all-too-common, serious and costly medical condition, for which no approved treatments currently exist beyond supportive care.

About AC607

AC607 is a novel biologic therapy under development for the treatment of AKI. AC607 also possesses potential applications in other grievous illnesses. AC607 comprises allogeneic bone marrow-derived mesenchymal stem cells that are harvested from healthy adult donors and then expanded via a mature and state-of-the art manufacturing process. AC607 homes to the site of injury where it mediates powerful anti-inflammatory and organ repair processes via the secretion of beneficial paracrine factors, without differentiation and repopulation of the injured kidney. Importantly, AC607 avoids recognition by the hosts immune system, enabling administration in an off the shelf paradigm without the need for blood or tissue typing.

About AlloCure

AlloCure, Inc. is a privately held, clinical-stage biotechnology company focused on the treatment of kidney disease. The company is a leader in the AKI field and is pioneering the development of the first effective therapy for the treatment of AKI. The companys headquarters is located in Burlington, MA. For more information about AlloCure, please visit the companys web site at http://www.allocure.com.

See the article here:
AlloCure Begins Phase 2 Clinical Trial in Acute Kidney Injury

BURLINGTON, Mass.--(BUSINESS WIRE)--

AlloCure, Inc. today announced that it has initiated a phase 2 clinical trial of AC607, the companys mesenchymal stem cell therapy, as a potential treatment for acute kidney injury (AKI). The randomized, double-blind, placebo-controlled, multi-center trial, designated ACT-AKI (AC607 Trial in Acute Kidney Injury) (NCT01602328), will enroll 200 cardiac surgery subjects at leading tertiary care centers in the United States.

ACT-AKI follows the positive results from a phase 1 AC607 trial in cardiac surgery subjects, which showed an excellent safety profile and encouraging data on the incidence of AKI and hospital length of stay, said Robert M. Brenner, M.D., AlloCure President and Chief Executive Officer. We have worked closely with leaders in the field on the design of ACT-AKI, and trial initiation represents an important milestone for AlloCure and the patients we collectively serve.

AC607 is a promising therapeutic candidate for AKI, for which effective therapies are greatly needed, said Richard J. Glassock, M.D., Emeritus Professor of Medicine at the Geffen School of Medicine at the University of California, Los Angeles. The initiation of ACT-AKI represents a critical step in the development of an innovative therapy for this all-too-common, serious and costly medical condition, for which no approved treatments currently exist beyond supportive care.

About AC607

AC607 is a novel biologic therapy under development for the treatment of AKI. AC607 also possesses potential applications in other grievous illnesses. AC607 comprises allogeneic bone marrow-derived mesenchymal stem cells that are harvested from healthy adult donors and then expanded via a mature and state-of-the art manufacturing process. AC607 homes to the site of injury where it mediates powerful anti-inflammatory and organ repair processes via the secretion of beneficial paracrine factors, without differentiation and repopulation of the injured kidney. Importantly, AC607 avoids recognition by the hosts immune system, enabling administration in an off the shelf paradigm without the need for blood or tissue typing.

About AlloCure

AlloCure, Inc. is a privately held, clinical-stage biotechnology company focused on the treatment of kidney disease. The company is a leader in the AKI field and is pioneering the development of the first effective therapy for the treatment of AKI. The companys headquarters is located in Burlington, MA. For more information about AlloCure, please visit the companys web site at http://www.allocure.com.

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AlloCure Begins Phase 2 Clinical Trial in Acute Kidney Injury

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/cwsq7k/stem_cells) has announced the addition of John Wiley and Sons Ltd's new book "Stem Cells" to their offering.

This third in the Current Topics in Molecular Cell Biology and Molecular Medicine Series contains a careful selection of new and updated, high-quality articles from the well-known Meyer's Encyclopedia, describing new perspectives in stem cell research. The approximately 40 chapters are divided into four sections: Basic Biology, Stem Cells and Disease, Stem Cell Therapy Approaches, and Laboratory Methods, with the authors chosen from among the leaders in their respective fields.

The two volumes represent an essential guide for students and researchers seeking an overview of the field.

Key Topics Covered:

Introduction to Stem Cells

Basic Biology

Stem Cells, Embryonic

Stem Cells, Adult

Stem Cells in the Adult Brain: Neurogenesis

Read the original post:
Research and Markets: Stem Cells - Current Topics in Molecular Cell Biology and Molecular Medicine Series

Professor Armin Curt, leading the study, described the result as fundamental.

He said: To find something that can repair the spinal cord is a huge breakthrough. If we can show that something has changed for the better [as a result of stem cell therapy] thats fundamental.

He presented the findings at the annual conference of the International Spinal Cord Society in London on Monday.

Prof Curt was working in partnership with StemCells Inc., a Californian company which also has a base in Cambridge.

Dr Stephen Huhn, from the firm, said: We think these stem cells are one of the first tools we have for actually repairing the central nervous system.

"To see this kind of change in patients who truly have the worst-of-the-worst type of injury to the spinal cord is very exciting."

The three patients, who all had complete spinal injury where they could feel nothing below the break, were each given a dose of 20 million adult neural stem cells about six months ago.

This was primarily a safety trial, and Prof Curt said monitoring had shown a very good safety profile.

But detailed questioning and objective tests also showed signals were passing up the injured spine to the brain, when they had not before.

One of the patients, Knut lstad, a 46-year-old Norwegian financial consultant, said: Ive noticed changes. When somebody touches my stomach, I can feel something. I cant be specific, but I can sense it.

Continued here:
Stem cells help paraplegics regain feeling

3 September 2012

Scientists in Glasgow are using stem cells to develop orthopaedic implants that could be considerably stronger and more durable than current products.

The team from Glasgow University and Southern General Hospital has designed a plastic surface that encourages bone cells to grow around it and so could be used to strengthen the bond between an implant and a patients bone.

Mesenchymal stem cells found in bone marrow can divide into other types of cells such as skin, muscle or bone when they receive the correct messages from the body. Glasgows surface would replace these messages to encourage bone growth.

The surface, created at Glasgow Universitys James Watt Nanofabrication Centre, is covered in tiny pits 120 nanometres across, said researcher Dr Matthew Dalby in a statement.

When stem cells are placed onto the surface, they grow and spread across the pits in a way that ensures they differentiate into therapeutically useful cells.

This will help the implant site repair itself much more effectively than has ever been possible before and could well mean that implants will last for the rest of a patients life.

Conventional implants made from polyethylene, stainless steel, titanium or ceramic dont have this kind of surface and so the stem cells around them typically divide into soft tissue which, combined with the natural loss of bone density that occurs as people age, can weaken the bond between the implant and the body.

The researchers want to manufacture the implants from an advanced polymer known as PEEK-OPTIMA, made by UK firm Invibio Biomaterial Solutions, to ensure they are as strong as possible.

One of the main selling points of PEEK is that it is very strong, has excellent stability and is very resistant to wear, said researcher Dr Nikolaj Gadegaard.

View original post here:
Stem cells could mean stronger orthopaedic implants

Public release date: 2-Sep-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

"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," said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLA's Jonsson Comprehensive Cancer Center. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life."

The research team was "intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life," said Crooks, a professor of pathology and pediatrics.

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, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack." said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

Read more from the original source:
UCLA researchers discover missing link between stem cells and immune system

ScienceDaily (Aug. 31, 2012) UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

"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," said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLA's Jonsson Comprehensive Cancer Center. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life."

The research team was "intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life," said Crooks, a professor of pathology and pediatrics.

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, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack." said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said

Once the lymphoid primed progenitor had been identified, Crooks and her team studied how gene expression changed during the earliest stages of its production from stem cells.

More:
'Missing link' between stem cells and the immune system

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.

Source:
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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.

Source:
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Four researchers are appealing
rejection of their proposals to win millions of dollars from the
California stem cell agency just as the agency is moving to curb such
reconsideration efforts by scientists.

Source:
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The $3 billion California stem cell
agency on Tuesday released details of proposed, major changes in how
scientists are allowed to appeal decisions when their
applications for millions of dollars are rejected by grant reviewers.

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

“So a project that was really going
to go into patients was essentially triaged.”

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Researchers from the University of
Southern California are making a pitch to overturn rejection of their
$20 million grant application by reviewers in one of the signature
commercialization rounds of the California stem cell agency.

“We are submitting the petition at
this time as we are new to the CIRM ICOC(governing board) process and after listening
to the July 26 ICOC meeting deliberations now understand that the
petition process allows the ICOC to further consider our proposal.
We noted that the proposal scored one point above ours and another
two points below ours, each utilized the extraordinary petition
strategy to gain ICOC review which resulted in funding approval in
the former, and reconsideration in the latter instance.”

“I'm not really quire sure that all
of the applicants clearly understood that they could come back to us
to address the criticisms(of reviewers).”

Concerns about whether all applicants fully understand the appeal process have surfaced on a number of occasions over the last several years. The CIRM board, however, is generally reluctant to overturn negative recommendations by reviewers. It also almost never reverses positive recommendations.

Source:
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Directors of the California stem cell
agency next week are expected to make unspecified changes in how
scientists can appeal denials of their applications for millions of
dollars in research grants.

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