New Technology from Asymmetrex Promises to End the Era of “Elusive” Adult Tissue Stem Cells

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This week an accepted-ahead-of-print report published online in the journal Stem Cell Research describes the development of a new technology from the stem cell technology start-up Asymmetrex that promises to move stem cell biology and biomedicine into a new quantitative era. Two commercially available antibodies can be used to specifically identify adult tissue stem cells for the first time.

Example of H2A.Z (yellow) identification of a hair follicle tissue stem cell nucleus.

It will be as if tissue stem cell biology put on glasses for the first time.

James Sherley, Director of the new biotech start-up Asymmetrex, LLC (previously, the Adult Stem Cell Technology Center, LLC) says that he is looking forward to laboratories around the globe evaluating the company’s most recent exciting new stem cell technology, which allows tissue stem cells to be counted for the first time. The new technology is reported online this week in Stem Cell Research.

With only the purchase of two commercially available antibodies, any basic cell biology lab can evaluate the new technology for counting its favorite adult tissue stem cells, which Asymmetrex also refers to as distributed stem cells. Asymmetrex scientists accomplished the essential proof of principle in the report with cultured mouse hair follicle stem cells. They also showed that cells with the specific detection criterion were found in mouse hair follicles themselves in regions known to contain the stem cells. With collaborator Dr. Jennifer Chen, they demonstrated that cells in experimental cultures enriched for human skeletal muscle stem cells had the criterion, too. The technology is predicted to be universally able to count adult tissue stem cells in many different tissue types and different vertebrate species, including most, if not all, human tissues.

To count tissue stem cells, the first antibody needed is one that identifies chromosomes found in all cells about an hour before they divide to become two cells. The second antibody needed is one that identifies a special set of chromosomes that is found specifically in adult tissue stem cells. Asymmetrex’s Director Sherley spent the last 16 years defining properties of these unique chromosomes, which are called immortal chromosomes. By evaluating both of these antibodies’ cell detection patterns simultaneously, adult tissue stem cells can be identified with sufficient specificity to count them with a high degree of confidence.

The new report shows that getting to the new technology was a rather complicated business. The project started with the work of Dr. Minsoo Noh when he was a doctoral graduate student in Dr. Sherley’s lab at the Massachusetts Institute of Technology. In his graduate studies, Dr. Noh applied a bioengineering-bioinformatics approach to identifying genes that were highly associated with the unique properties of adult tissue stem cells. To avoid the previously unsolved problem of impure tissue stem cells, Dr. Noh used a family of cells that were engineered to model the unique properties of tissue stem cells. He was successful in identifying a large number of cellular genes whose expression was highly specific for unique tissue stem cell properties.

With Dr. Noh’s success, the research team now faced a common bioinformatics pitfall – too many genes to know which to study next. Dr. David Winkler’s group at CSIRO in Australia, co-authors of the report, provided a solution. The new report details how Winkler’s team applied a newly emerging probabilistic approach to reduce a thousand-plus member gene set down to a single gene for interrogation, the histone H2A variant H2A.Z. Oddly, H2A.Z was reduced during adult tissue stem cell specific functions, which went against the conventional biomarker concept of being increased. Dr. Yang Hoon Huh, then a post-doctoral fellow with the Sherley team, undertook an intent investigation of H2A.Z’s tissue stem cell-associated properties despite its non-conformist expression. Due to his persistent studies, H2A.Z emerged as the key target of the second antibody in the new technology.

The ability to identify adult tissue stem cells specifically means that now, for the first time, they can be counted. This long awaited capability will begin a new era of quantitative stem cell biology and stem cell medicine. Sherley predicts that, “It will be as if tissue stem cell biology put on glasses for the first time.” Previously, tissue stem cell research, existing stem cell medicine (e.g., bone marrow transplantation), and new regenerative medicine developments have operated in a blurry world of not knowing the actual number of the elusive tissue stem cells involved in experiments or transplantation treatments. The ability simply to count the critical cells will have a major impact on the quality and progress of these important applications for continuing advances in medicine and human health.

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Asymmetrex, LLC is a Massachusetts life sciences company. Asymmetrex’s founder and director, James L. Sherley, M.D., Ph.D. is the foremost authority on the unique properties of adult tissue stem cells. The company’s patent portfolio contains biotechnologies that solve the three main technical problems – production, quantification, and monitoring – 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. Currently, Asymmetrex is employing its technological advantages to pursue commercialization of facile methods for monitoring adult tissue stem cell number and function.

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James L. Sherley, M.D., Ph.D.
Asymmetrex, LLC
+1 (617) 990-6819
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