Researchers identify a promising biomarker to screen stem cell quality

Published recently in the Stem Cells journal, a new study addresses a major issue that has been challenging the human mesenchymal stem cells (hMSCs) therapy.

Although scores of clinical trials involving an unlimited number of patients are ongoing to test the ability of hMSCs to treat everything from brain injury to heart disease, no method is available to determine whether it was worthwhile to subject the donor to a painful and costly surgical harvesting of bone marrow.

But this latest research, performed by researchers at the Agency for Science, Technology, and Research (A*STAR), Singapore, has identified a promising biomarker for prescreening donors for the growth capacity and potency of their MSCs.

With the global stem cell market predicted to reach over US$270 billion by 2025 (according to a report published by Transparency Market Research), there is a pressing need for effective biomarkers to be used in the screening of stem cells from prospective donors. This need is boosted by the rapid growth of regenerative medicine, with its pallet of cells, genes and engineered tissues.”

Dr Simon Cool, Study Co-Corresponding Author, Institute of Medical Biology, Agency for Science, Technology and Research

That is what triggered this recent analysis.

In previous research, this same laboratory had categorized hMSCs from age as well as sex-matched human donors into low- and high-growth capacity groups and ascertained criteria for detecting stem cells that have improved potency.

These hMSCs showed increased proliferative potential that correlated with enhanced clonogenicity, a higher proportion of smaller-sized cells with longer telomeres, elevated expression of certain cell surface markers, and most importantly, improved ability to mediate ectopic bone formation.”

Lawrence Stanton, PhD, Study Co-Corresponding Author, Qatar Biomedical Research Institute

Stanton was a member of A*STAR’s Genome Institute of Singapore at the time of the study.

The researchers’ recent analysis sought to build on that data by conducting molecular analyses of these stem cells, so that a better understanding can be obtained about factors that were responsible for their enhanced utility.

Microarray analysis demonstrated that hMSCs with genomic deletion of glutathione S-transferase theta (GSTT1)—belonging to a superfamily of genes that bring together toxins and glutathione to safely eliminate them from the body—exhibit high growth capacity.

The GSTT1-null hMSCs also display an improved ability to clone independently and develop into full colonies; they also have longer telomeres. These two factors are significant determinants of MSC potency.

We believe our study highlights the utility of GSTT1 as a potential biomarker for MSC scalability and may prove useful in selecting potential donors for the creation of high quality hMSC cell banks to improve stem cell therapies.”

Dr Simon Cool, Study Co-Corresponding Author, Institute of Medical Biology, Agency for Science, Technology and Research

According to Dr. Jan Nolta, Editor-in-Chief of Stem Cells, “The ability to pre-screen donors for a marker that corresponds to better growth of MSCs in vitro is truly important.”

Many teams have sought screening tools like this, which could prevent lot failure for clinical batches of MSCs that don’t expand robustly. Until now, there has been no way to evaluate that prior to marrow harvest,” Dr. Nolta concluded.

Source:
Journal reference:

Sathiyanathan, P., et al. (2020) A genomic biomarker that identifies human bone marrow-derived mesenchymal stem cells with high scalability. Stem Cells. doi.org/10.1002/stem.3203.

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