The future of regenerative medicine has never looked brighter. Ongoing clinical trials for treatments using stem cells—cells that have the potential to develop into a variety of tissue types—are giving hope to patients with conditions ranging from autoimmune to neurodegenerative diseases.
Many clinically explored cell-based therapies use mesenchymal stem cells (MSCs) isolated from human donors, and these MSCs vary greatly in terms of quality and growth potential. To comply with clinical requirements, a time-consuming and expensive screening step is required after harvesting to assess their quality.
Seeking to find a biomarker that can identify high-quality MSCs more efficiently, Simon Cool, a Research Director at A*STAR’s Institute of Molecular and Cell Biology (IMCB), and collaborators from A*STAR’s Genome Institute of Singapore (GIS) compared the molecular profiles of donor MSCs placed in two groups: high- or low-growth potential.
“A biomarker that can accurately predict the quality and scalability of MSCs from donors before harvest would represent a major breakthrough in stem cell manufacturing,” Cool said.
In microarray studies of donor MSCs, the researchers found a striking difference in the expression of the GSTT1 gene, which codes for glutathione S-transferase theta 1, a member of a superfamily of metabolic enzymes. Most MSCs with high-growth potential did not express GSTT1 due to a gene deletion.
Next, the researchers used RNA interference—a technique that uses RNA molecules to inhibit gene expression—to confirm that MSCs lacking GSTT1 expression grew more rapidly, with enhanced clonogenicity and longer telomeres. Importantly, these MSCs did not lose their ‘stemness.’ The researchers have filed a patent based on these findings.
“We were surprised that what started as an unbiased molecular screen of MSCs with high- versus low-growth capacity resulted in the identification of a single but robust DNA biomarker,” Cool said.
The critical next step is to assess the safety of rapidly growing cells. The researchers are in the process of determining whether the MSCs maintain an appropriate immune profile and retain stable genomic DNA.
Simultaneously, they are developing a diagnostic kit that can rapidly determine the genetic makeup of donors, which would support the banking of allogeneic stem cells for therapeutic use. They are also in the process of identifying additional biomarkers beyond GSTT1, which appears to be the most promising candidate so far.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB), the Institute of Medical Biology (IMB) and the Genome Institute of Singapore (GIS).
