A study published in June in STEM CELLS addresses a significant problem that has been confronting human mesenchymal stem cells (hMSCs) therapy. While hundreds of clinical trials involving thousands of patients are under way to test hMSCs' ability to treat everything from heart disease to brain injury, there has been no way to determine prior to the donor undergoing a painful and expensive surgical harvesting of bone marrow whether or not it would be worth the effort. This new study identifies a potential biomarker for prescreening donors for their MSCs' growth capacity and potency.
In an earlier study, the researchers classified hMSCs from age and sex-matched human donors into high- and low-growth capacity groups and established criteria for identifying stem cells with enhanced 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 improved ability to mediate ectopic bone formation.
The latest study sought to build upon that information by performing molecular analyses of these cells 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.
The 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, the researchers say.