Produce Greater Numbers of Therapeutic Adult Tissue Stem Cells at Reduced Cost

by Asymmetrex on August 29, 2017

For many years, progress in stem cell medicine has been held back because of a lack of effective and efficient methods for the manufacture of therapeutic adult tissue stem cells. Massachusetts stem cell biotechnology company Asymmetrex announces this week that it now offers a new contract service that can help suppliers of therapeutic adult tissue stem cells produce significantly more stem cells at greatly reduced cost.

Asymmetrex Introduces New Contract Service to Produce Greater Numbers of Therapeutic Adult Tissue Stem Cells at Reduced Cost

Today, Asymmetrex, the Massachusetts based stem cell biotechnology innovator, begins offering a new contract service to support the cell therapy industry’s production of therapeutic adult tissue stem cells. Stem cells are a small sub-population of specialized cells that function to renew and repair the organs and tissues of children and adults. Stem cells from a healthy donor can be transplanted to restore or repair diseased or damaged organs and tissues in patients who are sick or injured.

Stem cell transplant treatments do not require expansion of donor stem cells when a donor with a compatible immune system is available for a patient. However, in general, there are many more patients in need of a transplant than there are immune compatible donors. So, the future ability of stem cell medicine to address the full degree of medical need depends on developing the ability to expand initial donor stem cell populations into larger numbers without loss of their curative properties. Expanded numbers of quality adult tissue stem cells are also needed to support statistically sound clinical trials for continued development of stem cell transplant therapies.

Asymmetrex’s new advance for cell therapy suppliers is the result of the company’s unique proprietary expertise in adult tissue stem cell culture. Its recently patented AlphaSTEM Test™ technology, which is a means to count adult tissues stem cells specifically for the first time, is based on the earlier discovery that during expansion in culture, ironically, adult tissue stem cells are lost as a result of their intrinsic tissue renewal property. Under typical culture conditions, stem cells continuously produce non-stem cells that subsequently undergo significant, though limited, multiplication. However, as in the body, stem cells do this while not multiplying their own number. The result of these continued natural processes in culture is progressive dilution and loss of the stem cells with each subsequent expansion culture.

Recently, Asymmetrex demonstrated that not only can its AlphaSTEM Test™ technology be used to count and certify the quality of adult tissue stem cells, but it can also be used to establish unique culture conditions projected to reduce stem cell dilution significantly during expansion. Asymmetrex’s Director, James L. Sherley, M.D., Ph.D., shares, “Two years ago when we achieved specific counting, I expected that we would be able to find conditions for increasing stem cell number, too; but even I didn’t anticipate the projected huge savings in production costs!” The company’s projections indicate that it can achieve production of twice as many stem cells as several companies have reported, but require only 5% or less of their production cost. The required culture time is also reduced significantly.

The new service has been developed first for human mesenchymal stem cells, which are found in a variety of tissues including bone marrow, adipose (fat), umbilical cord, and amniotic fluid. These cells are an ideal first focus, as there are many companies worldwide working on their production to supply hundreds of stem cell transplantation clinical trials each year. Asymmetrex plans to also investigate application of the method to other types of adult tissue stem cells, which have been largely dismissed for expansion because their donor populations are not as proliferative as mesenchymal stem cells. Sherley says that blood stem cells are a very important member of this latter group on the Asymmetrex horizon.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrex’s founder and director, James L. Sherley, M.D., Ph.D., is an internationally recognized expert on the unique properties of adult tissue stem cells. The company’s patent portfolio contains biotechnologies that solve the two main technical problems – quantification and production – that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Asymmetrex markets the first technology for determination of the dose and quality of tissue stem cell preparations (the “AlphaSTEM Test™”) for use in stem cell transplantation therapies and in pre-clinical assays for drug safety. The same technology underpins Asymmetrex’s contract service for optimizing manufacturing processes for therapeutic adult tissue stem cells.

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AsymmetrexProduce Greater Numbers of Therapeutic Adult Tissue Stem Cells at Reduced Cost

Asymmetrex Joins RegMedNet Panel to Discuss Cell Therapy Regulation

by Asymmetrex on June 22, 2017

In an online forum scheduled for June 27, 2017, the regenerative medicine social media network RegMedNet will sponsor a panel discussion on emerging developments in the global landscape of government regulations for stem cell medical research. Asymmetrex, a company developing new methods for specifically quantifying adult tissue stem cells, will provide expertise on the panel for the impact of a new emerging technology for determining the quality and dose of adult tissue stem cell treatments.

Asymmetrex Joins RegMedNet Panel to Discuss Cell Therapy Regulation

For the months of May and June, United Kingdom-based social media network RegMedNet has produced a Spotlight series on “Cell Therapy Regulation” for its regenerative medicine followship. The series has featured scholarly reviews and perspectives by leading experts on the unique regulatory challenges of stem cell medical research.

Stem cell clinical trials present unique regulatory challenges that are not an issue in conventional pharmaceutical and biopharmaceutical clinical research. On the one hand, introducing patients’ own cells, and even cells from matched donors, so far has been observed to be a relatively safe medical procedure. However, the small numbers of patients enrolled in clinical trials thus far have precluded evaluations of the reproducibility of efficacious effects associated with some transplanted cells.

The Spotlight takes a global look at current and changing regulatory policy for stem cell medical research. Experts review and evaluate recent policy developments for government agencies in the U.S., Europe, Japan, Canada and other countries.

On June 27, the Spotlight series will feature an online panel discussion of the topic. Panelists include leaders in companies and agencies that support development of cell therapeutics. James L. Sherley, M.D., Ph.D., Director of Asymmetrex, is one of the invited panelists. Sherley adds a perspective that has been missing from recent panels of this type on many different aspects of cell therapy, in particular, cell therapy regulatory policy.

An important role for medical research regulatory policy is ensuring the quality of evaluated prospective medicines. In the case of regenerative stem cell medicine, meeting this charge was not fully possible previously. No suitable methods existed for quality control evaluation of the essential stem cells in treatment samples. Asymmetrex now markets a technology for this purpose. On the panel, Sherley will address how the availability of a means for determining treatment stem cell quality and dose may impact future developments in stem cell medical research regulatory policies.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrex’s founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The company’s patent portfolio contains biotechnologies that solve the two main technical problems – production and quantification – that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Asymmetrex markets the first technology for determination of the quality and dose of tissue stem cell preparations (the “AlphaSTEM Test”) for use in stem cell transplantation therapies and in pre-clinical assays for drug safety.

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AsymmetrexAsymmetrex Joins RegMedNet Panel to Discuss Cell Therapy Regulation

Asymmetrex’s Head Will Lead Discussion on Supplying Private Stem Cell Clinics

by Asymmetrex on March 7, 2017

On March 8-9 in Boston, stem cell medicine biotechnology start-up Asymmetrex will take the lead in introducing a potentially controversial topic to attendees at the 6th Annual Clinical Trials Supply New England 2017 conference. Executives from contract research organizations that supply companies running FDA-approved stem cell clinical trials will be presented with the proposition of promoting advances in stem cell medicine by also supplying private clinics that offer medical treatments with adult tissue stem cells.

Recent scientific reports put the number of private clinics offering stem cell medical treatments in the U.S. at greater than 400. More than 300 of these clinics emerged since 2009. They mirror the rapid increase in FDA-approved clinical trials during the same period at a rate of about 300 new therapy-focused adult tissue stem cell trials each year. However, because of the inherently small number of patients enrolled in early clinical trials and the much larger number of patients seen in medical clinics, the number of stem cell treatments performed in private clinics dwarfs the number in clinical trials by more than 10-fold.

In both settings, treatment cell transplants per se appear generally safe, as long as proper care is given to other routine safety factors, which include mainly keeping treatments free of infectious agents and chemical contaminants and avoiding immune reactions. These safety procedures fall well within the training and expertise of physicians in private clinics, as well as in hospital-based clinical trials.

The rapid growth of private stem cell clinics has alarmed some stem cell scientists and their member organizations. The clinics are accused of making false claims, exploiting patients’ pain and distress for financial gain, and generally harming the reputation of stem cell science. In contrast, in FDA-approved clinical trials, patient volunteers are necessarily informed that their treatments are experimental, and therefore may bring them no medical benefit. Generally, trial subjects do not pay for their treatment, though often treatment costs are covered by their personal health insurance.

Asymmetrex’s founder and director, James L. Sherley, M.D., Ph.D., recently began a public discourse, in which he argues that in the important respects private stem cell clinics are not all that different than FDA-approved clinical trials. First, he says that glibly painting all several hundred or more private stem cell clinics as exploitive is an unsubstantiated claim itself. Generally, physicians in both settings are diligently looking for ways to improve the health of patients – clinical trial physicians in the more distant future and private clinic physicians immediately. Sherley, a physician scientist, stresses the importance of recognizing medical empiricism as an important contributor to the advance of modern medicine and medical science.

At the conference, Sherley is scheduled to lead a panel discussion on the topic on March 8 at 15:50 PM (EDT) and give a talk on March 9 at 13:30 PM (EDT). A major new position he will present is that the volume of stem cell treatments now occurring in private clinics is much too large to simply disparage and attempt to shut down. Working to improve the quality of private stem cell clinic treatments for patients and to improve their documentation towards accelerating progress in stem cell medicine is a better goal.

To attendees at this week’s Clinical Trials Supply conference, Sherley will suggest that the supply of private stem cell clinics with high quality, certified sources of stem cells is an underappreciated crucial need for advancing stem cell medicine. The companies that are able to mobilize to fill in this supply gap could have a 10-fold greater impact on advancing stem cell medicine compared to their current minimal impact in FDA-approved stem cell clinical trials.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrex’s founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The company’s patent portfolio contains biotechnologies that solve the two main technical problems – production and quantification – that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrex’s focus is employing its technological advantages to develop and market facile methods for monitoring adult stem cell number and function in stem cell transplantation treatments and in pre-clinical assays for drug safety.

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AsymmetrexAsymmetrex’s Head Will Lead Discussion on Supplying Private Stem Cell Clinics

Asymmetrex Says to Intellia Therapeutics, “Don’t Forget the Stem Cells. Call Us”

by Asymmetrex on August 23, 2016

The biotech medicine world has been waiting to hear from new gene-editing companies exactly how they will go about turning the highly touted research advance into an effective medical advance. If reports about gene-editing company Intellia Therapeutics’ plan are any indication of the approach that will be taken, there is a rocky road ahead for sure.

Intellia seems to be following the approach of companies like Alnylam by focusing first on getting efficient transfer of their gene-editing machines into liver cells.  This approach has worked well so far for Alnylam in early clinical trials designed to reduce the levels of disease-causing proteins by blocking their production with RNAi molecules.  However, Intellia seems to be overlooking a very fundamental difference between Alnylam’s RNAi drugs and Intellia’s gene-editing “drugs.”

Alnylam’s drugs work directly in mature liver cells.  If they need repeated dosing, there is nothing inherent in their action that would preclude continued dosing for a patient’s lifetime.  In contrast, Intellia would be quite concerned if they needed to do multiple dosing because their gene-editing machines could make quite a bit of trouble, even potentially disrupting earlier edits.  But, Intellia is reporting now because they are quite pleased by how effective their molecular machines seem to be at editing a targeted gene expressed abundantly by mature liver cells.

Here at Asymmetrex, we were looking for one more crucial piece of information for Intellia.  Intellia does not report how long the editing effect lasts.  If they have only targeted mature liver cells, it will not last for long.  In about 200 days, ALL of the mature cells in the liver are replaced by new mature cells produced by the division of liver tissue stem cells.  If the liver is injured (e.g., by other medicines, dietary toxins, or infection), the replacement of mature liver cells can be even faster.  So, to achieve long lasting gene-editing therapy and avoid the need for undesirable multiple dosing, Intellia must put its gene-editing machines into liver tissue stem cells.  Alnylam’s drugs don’t have this requirement.

The liver has one of the highest estimated stem cell fractions.  But, still, only about one in 250 cells are estimated to be stem cells.  So, getting a high fraction of them edited is a certain challenge in the future of Intellia.  Since there are no specific markers reported that would allow targeting gene-editing machines to liver stem cells and not mature liver cells, the road ahead is even rockier.  However, there is one company that has a path to the discovery of such markers, which may be crucial to Intellia’s success. Asymmetrex is waiting for their call. 

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AsymmetrexAsymmetrex Says to Intellia Therapeutics, “Don’t Forget the Stem Cells. Call Us”

Source of liver stem cells identified

by Asymmetrex on August 18, 2015

Source of liver stem cells identified


 “We’ve solved a very old problem,” says Roel Nusse, an HHMI investigator at Stanford University who led the research.

Asymmetrex says, “Wait a minute!  Hold that phone call for at least a moment, please!”  The new evidence for homeostatic stem cells located around central veins in the liver does not solve an old problem.  Instead, it creates a new one, which the authors are either unaware of or are ignoring.  The manuscript is careful to acknowledge that the newly described putative stem cells do not repopulate the entire liver.  That characteristic itself should evoke suspicions about the nature of the cells, because a basic property that defines homeostatic adult tissue stem cells is the ability to repopulate an entire tissue.

More to the point, the authors do not square away their new findings with earlier studies that used cell kinetics techniques to identify cells in the anatomically opposing peri-portal region with properties indicative of repopulating the entire liver with two lineages of liver-specific cells, hepatocytes and biliary epithelium cells.  In stark contrast to the new report, the hepatocyte descendants of peri-portal adult liver stem cells die at the central vein.

Asymmetrex also warns of the common negligence of not considering the potential for cellular artifacts due to the molecular genetic manipulations employed in stem cell lineage-tracing studies, as in this one, should be cause for greater caution in interpretation.  As such, evaluating the lineage-tracing mice for liver tumors could prove particularly informative regarding what is going on in this intriguing model.


 

Original Article Science Daily

Howard Hughes Medical Institute (HHMI) scientists have identified stem cells in the liver that give rise to functional liver cells. The work solves a long-standing mystery about the origin of new cells in the liver, which must constantly be replenished as cells die off, even in a healthy organ.

“We’ve solved a very old problem,” says Roel Nusse, an HHMI investigator at Stanford University who led the research. “We’ve shown that like other tissues that need to replace lost cells, the liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease.” Nusse and his colleagues reported their findings August 5, 2015, in the journal Nature.

The liver is made up mostly of hepatocytes, highly specialized cells that carry out the organ’s many tasks, including storing vitamins and minerals, removing toxins, and helping regulate fats and sugars in the bloodstream. As these cells die off, they are replaced by healthy new hepatocytes. The source of those new cells had never been identified, Nusse says.

Stem cells, which replenish their own populations and maintain the ability to develop into more specialized cells, provide new cells in the skin, blood, and other tissues where cells are naturally lost over time. But no stem cells had been found in the liver. Some scientists speculated that mature hepatocytes might maintain their populations by dividing. But Nusse says the mature cells have become so specialized to carry out the work of the liver, they have likely lost the ability to divide.

“Differentiated hepatocytes have amplified their chromosomes,” he explains. That is, the cells have more than the usual two copies of every chromosome. “This enables the cells to make more proteins, but it really compromises their ability to divide.”

Nusse’s lab at Stanford focuses on a family of proteins of called Wnts, which are key regulators of stem cell fate. To find and follow stem cells in a variety of tissues, they have developed mice in which cells that respond to the Wnt signal are labeled with a fluorescent protein. Several years ago, they decided to use the mice to search for stem cells in the liver.

Bruce Wang, a gastroenterologist at the Liver Center at the University of California, San Francisco, led the experiments as a visiting scholar in Nusse’s lab. Wang began by searching for fluorescently labeled, Wnt-responsive cells in the livers of the engineered mice, and he ultimately found them clustered around the liver’s central vein.

Once they knew which cells to focus on, the scientists tracked the fluorescently labeled cells’ behavior. Over time, they noticed that the cells they were tracking divided rapidly, steadily replenishing their own population. This was possible because unlike mature hepatocytes, the labeled cells had only two copies of each chromosome. By following the descendents of the stem cells for up to a year, the scientists discovered that these had changed, taking on the specialized features and amplified genomes of mature hepatocytes. “This fits the definition of stem cells,” Nusse says.

As expected, the liver stem cells required Wnt signals to maintain their stem cell identity. Nusse’s team discovered that endothelial cells lining the central vein, the blood vessel around which the stem cells were clustered, released Wnt molecules into the tissue. Stem cells that migrated out of reach of that signal quickly lost their ability to divide into new stem cells and began to develop into mature hepatocytes. Nusse says this is consistent with how stem cells are known to behave in other tissues.

The lab is now investigating how the newly identified stem cells might contribute to regeneration of liver tissue after injury. It will also be important to explore whether liver cancers tend to originate in these replicating cells, as opposed to more mature hepatocytes, Nusse says.

 

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AsymmetrexSource of liver stem cells identified

First Stem Cell-Based Approach to Treat Type 2 Diabetes

by Asymmetrex on May 8, 2015

First Stem Cell-Based Approach to Treat Type 2 Diabetes – A combination of human stem cell transplantation and anti-diabetic drugs proved to be highly effective at improving body weight and glucose metabolism in a mouse model of type 2 diabetes.

Article by ScienceDaily


“Heroic study, but modest findings.  #WeighTheFood.  Some data could be explained by differences in the appetites of mice after transplant and diabetes drugs.”  Asymmetrex, May 8, 2015


The findings, published March 19th by Stem Cell Reports, could set the stage for clinical trials to test the first stem cell-based approach for insulin replacement in patients with type 2 diabetes.Type 2 diabetes, which accounts for 90%-95% of the now approaching 400 million cases of diabetes worldwide, is currently treated by oral medication, insulin injections, or both to control blood glucose levels. However, insulin delivery is imprecise, onerous, and often promotes weight gain, while drugs do not work in some patients and may cause gastrointestinal problems or low blood glucose levels, highlighting the strong need for better treatment options.

To address this need, senior study author Timothy Kieffer of the University of British Columbia collaborated with BetaLogics, a division of Janssen Research & Development, LLC, and tested a promising stem cell transplantation approach.

First, they fed mice a high-fat diet to induce obesity, low responsiveness to insulin, and high blood glucose levels–the hallmarks of type 2 diabetes. The mice then received transplants of encapsulated pancreatic progenitor cells derived from human embryonic stem cells. These transplanted cells matured into insulin-secreting beta cells, resulting in improvements in insulin sensitivity and glucose metabolism. Moreover, stem cell transplantation combined with currently available antidiabetic drugs resulted in rapid weight loss in the mice and more significant improvements in glucose metabolism compared with either treatment alone.

Moving forward, the researchers will use their mouse model of type 2 diabetes to test the effectiveness of transplanting more mature insulin-producing cells that could potentially reverse symptoms of diabetes faster and at a lower dose compared to pancreatic progenitor cells.

A similar stem cell-based transplantation approach recently obtained clearance from the US Food and Drug Administration and Health Canada to be tested in patients with type 1 diabetes in phase1/2 clinical trials sponsored by a regenerative medicine company called ViaCyte.

“Success in these clinical trials could pave the way for testing in patients with type 2 diabetes,” Kieffer says. “Our hope is that a stem cell-based approach to insulin replacement will ultimately improve glucose control in patients with both type 1 and type 2 diabetes, resulting in healthier, longer lives.”

 

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AsymmetrexFirst Stem Cell-Based Approach to Treat Type 2 Diabetes