Researchers at the Agency for Science, Technology, and Research (A*STAR) in Singapore say they have identified a potential biomarker for prescreening donors for their human mesenchymal stem cells’ (MSCs) growth capacity and potency.
“With the global stem cell market predicted to reach over $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,” said Simon Cool, PhD, of A*STAR’s Institute of Medical Biology and co-corresponding author of the study “A Genomic Biomarker that Identifies Human Bone Marrow-Derived Mesenchymal Stem Cells with High Scalability” which appears in Stem Cells.
“Although the application of human mesenchymal stem cells (hMSCs) to repair damaged or diseased tissues has proven relatively effective, both the donor‐to‐donor variability in ex vivo expansion rates and the maintenance of stemness remain a bottleneck to widespread translation. Previous work from this laboratory stratified donors into those yielding hMSCs with high‐ or low‐growth capacity; global transcriptomic analysis revealed that high‐growth‐capacity hMSCs were characterized by a loss of the gene encoding glutathione S‐transferase theta 1 (GSTT1 ). These GSTT1 ‐null hMSCs demonstrated increased proliferative rates, clonogenic potential, and longer telomeres compared with low‐growth capacity hMSCs that were GSTT1‐ positive,” write the investigators.
“Thus, this study identifies GSTT1 as a novel genomic DNA biomarker for hMSC scalability. Expression of GSTT1 is haplotype‐specific. This study found that human bone marrow‐derived mesenchymal stem cells (hMSCs) containing a genomic deletion of GSTT1 show high growth capacity. The GSTT1 ‐null hMSCs also have enhanced clonogenicity and longer telomeres. Therefore, GSTT1 can be considered a genomic biomarker of hMSC scalability.”
The team’s latest investigation sought to build upon its previous work by performing molecular analyses of these hMSCs to better understand what accounted for their improved utility. Microarray analysis revealed that hMSCs with a genomic deletion of glutathione S-transferase theta (GSTT1), part of a superfamily of genes that bring together glutathione and toxins to safely remove them from the body, show high-growth capacity. The GSTT1-null hMSCs also exhibit an enhanced ability to clone themselves and grow into full colonies, and they have longer telomeres. Both of these factors are important 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,” noted Cool.