Stem Cell Toxicology & Regenerative Medicine Applications

Asymmetrex’s AlphaSTEM Technology Is A First-Ever Technology For Quantitative Analysis Of Adult Tissue Stem Cells That Will Accelerate Progress In Stem Cell Biomedicine

Click here to download a slide deck with the most recent technological benchmarks. Posted October 27, 2015

Overview

Asymmetrex, LLC and AlphaSTAR Corporation (ASC) have partnered to develop a first-of-its-kind computer simulation-primary cell culture technology with the capability of quantitative analysis of adult tissue stem cells. Because of their essential roles in normal organ and tissue function, initiation of diseases like cancer, and responses to medicines, effects on adult tissue stem cells are crucial determinants of success in tissue biology research, regenerative medicine, and drug development. This wide-ranging importance of adult tissue stem cells in biomedical research and medicine makes the longstanding unmet need for methods for their quantitative analysis all the more significant. The new “AlphaSTEM” technology provides, for the first time, the ability to quantify the number, viability, and unique tissue renewal function of adult tissue stem cells in research samples, treatment preparations, and drug evaluation assays. AlphaSTEM technology is ready for immediate deployment to estimate these important properties of adult stem cells in any mammalian tissue cell preparation, and in particular those from human subjects and patients.

The need – Quantifying adult tissue stem cell number and function

Adult tissue stem cells exist in small numbers in organs and tissue, and they are difficult to induce to multiply to higher numbers. These two inherent biological properties result in impure preparations when attempts are made to isolate and purify the cells. As a result, discovering biomarkers capable of specific identification of adult tissue stem cells has been an unyielding challenge. The best currently available tissue “stem cell biomarkers” are also expressed by the much more abundant lineage-committed progenitors that expand from the division of tissue stem cells. So, such biomarkers (e.g., CD34 and CD133) are unable to estimate even the relative stem cell number of different research samples or cell preparations for stem cell transplantation treatments (e.g., bone marrow transplantation). Being unable to estimate tissue stem cell number, these biomarkers are also unable to define the viability and the functional properties of tissue stem cells that might be present.

The solution – Breakthrough bioengineering embraces verified aerospace innovation

Asymmetrex, LLC was founded on fundamental knowledge of and bioengineering expertise for adult tissue stem cell kinetics, which encompass the processes by which tissue stem cells renew differentiating tissue cells and maintain their own number in mammalian tissues. Three years ago, Asymmetrex’s founder began a partnership with ASC to apply multivariate probabilistic computer simulation techniques to the problem of inferring tissue stem cell properties from primary tissue cell culture data. For over 20 years, ASC has innovated physics-based computer simulation software that determines the failure, failure modes, strength, life, and safety of complex advanced materials for the Aerospace Industry. ASC has won numerous awards, including for its investigative analysis of the Columbia Space Shuttle accident, which earned it NASA’s Group Achievement Award in 2004. This vast repository of computer simulation intellectual property was integrated with the adult stem cell kinetics bioengineering expertise of Asymmetrex to solve the adult tissue stem cell detection problem.

The product of this unique partnership is an innovative bioengineering approach that combines fundamental ideas in adult tissue stem cell multiplication modeling with computational simulation methods. The resulting AlphaSTEM technology estimates adult tissue stem cell number, viability, and tissue renewal function from an input of specially prescribed primary cell culture multiplication data. The software is based on a bioengineered mathematical model that describes the total cell multiplication output rates of mammalian tissue cell cultures in terms of the different subtypes of cells present (e.g., stem, lineage-committed, differentiated, dead) and their individual cell multiplication rates. AlphaSTEM technology can also be used to sensitively detect effects of exogenous additives (e.g., drugs) on tissue stem cell properties.

Applications

Tissue Stem Cell Toxicology: Early prediction of drug candidate failure could save $4 billion/yr

A crucial unmet need in the pharmaceutical industry is a convenient and effective method for assaying drug effects on tissue stem cells. In particular, drugs that are toxic to adult stem cells produce severely debilitating side effects. For example, the dose-limiting bone marrow failure induced by many cancer chemotherapy drugs is due to toxic effects against blood-forming tissue stem cells that reside in the bone marrow. Such toxicities can be life threatening, erasing any therapeutic benefits, and curtailing the commercial success of a promising new drug candidate. An estimated 20% of drugs that fail preclinical animal testing and initial Phase I and Phase II clinical trials do so because of intolerable toxicity. At least half of these failures have features of adult stem cell toxicity. These toxicities may even emerge after a new drug has successfully reached the marketplace. Some seemingly idiosyncratic deadly drug toxicities that emerge after a new drug has entered into general medical practice – with increasing numbers of patients and more extended doses – may also be related to chronic toxicity against adult tissue stem cells. So, tissue stem cell-toxic agents are a significant cause of expensive drug candidate failures. AlphaSTEM technology could identify these much earlier in the drug development process, leading to greatly reduced drug development costs, accelerated drug development, and increased drug safety. Current estimates indicate that full implementation of AlphaSTEM technology by major U.S. pharmaceutical companies could save the industry as much as $4 billion each year.

Regenerative Medicine: First-ever quality control for tissue stem cell transplantation treatments

AlphaSTEM technology can provide presently lacking quality control data for new regenerative medicine clinical trials as well as significantly improve approved stem cell transplantation treatments (e.g., cord blood and bone marrow transplantation). Currently, the most crucial factor for success in stem cell transplantation therapy – sufficient number of high functioning adult tissue stem cells – is an unknown throughout regenerative medicine practice. AlphaSTEM technology can fill this longstanding void. AlphaSTEM technology can also be used to identify agents that increase the therapeutic properties of adult tissue stem cells to improve the effectiveness of tissue stem cell transplantation treatments.

Tissue Stem Cell Research: A powerful new tool for education and training in tissue cell biology

The AlphaSTEM simulation software is an exciting new advance for instruction of undergraduate and graduate students in the fundamental principles of mammalian tissue cell biology. In particular, the software allows students to conduct virtual experiments to evaluate how different properties of stem cells and other tissue cells factor in normal tissue function and the development of diseases like cancer, diabetes, and liver failure. The AlphaSTEM software is also unique in its potential to predict patient responses to drug candidates based on their tissue cell targets of action.

 

State of the technology – Ready for immediate application

The development of the AlphaSTEM computer simulation software is completed, and the essential technological benchmarks have been achieved using it. The technology very accurately describes primary tissue cell culture data in the published literature, which in one case had previously defied explanation for more than five decades. New cell culture data were also used to validate AlphaSTEM technology’s ability to precisely simulate the cell multiplication output data of pre-senescent human lung cell cultures and Asymmetrex’s expanded human liver cell strain cultures.

AlphaSTEM’s ability to use specialized cell culture data to detect changes in the number and function of human liver tissue stem cells was confirmed by comparing growth data from control human liver cell cultures and cultures supplemented with the purine nucleoside xanthosine. In independent studies, Asymmetrex scientists have shown that xanthosine increases self-replication by adult tissue stem cells leading to their exponential expansion. AlphaSTEM technology very clearly discerned this effect of xanthosine in human liver cell cultures.

 The opportunity – AlphaSTEM technology is poised to accelerate stem cell biomedicine

Asymmetrex and ASC are open to discussing early adoption of AlphaSTEM technology with institutions and companies in all spheres of stem cell biomedicine. These include research universities and institutes, biotechnology industry, pharmaceutical and biopharmaceutical industry, and regenerative medicine groups. In particular, pharmaceutical and regenerative medicine companies constitute major commercialization targets because of the immediate positive impact that implementation of AlphaSTEM technology is predicted to have on their business success.

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