A groundbreaking study led by researchers from Nara Institute of Science and Technology in Japan has identified a potential solution to one of the major challenges in stem cell therapy: the risk of tumor formation after transplantation.
The research, published in Stem Cells Translational Medicine, focuses on a membrane protein called EPHA2, which may be key to developing safer regenerative therapies. Pluripotent stem cells (PSCs) have long been of interest due to their ability to self-renew and differentiate into various cell types, offering hope for repairing damaged organs. However, the risk of tumorigenesis has been a significant obstacle in translating this potential into clinical applications.
The research team discovered that EPHA2 plays a crucial role in maintaining stem cells in an undifferentiated state. They found that EPHA2 co-exists with OCT4-a, a transcription factor essential for embryonic stem cell differentiation. When the EPHA2 gene was silenced, stem cells spontaneously differentiated, suggesting its importance in preserving stem cell potency.
Building on this finding, the researchers hypothesized that EPHA2-expressing stem cells might be responsible for tumor formation after transplantation. To test this, they induced differentiation in PSC cultures, removed EPHA2-positive cells using a magnetic antibody, and transplanted the remaining cells into mice. The results showed a significant reduction in tumor formation compared to transplants containing EPHA2-positive cells.
This breakthrough suggests that EPHA2 could serve as a marker for identifying and removing undifferentiated stem cells before transplantation, potentially reducing the risk of tumorigenesis in regenerative treatments. The findings bring us closer to developing safer protocols for using PSCs in regenerative medicine, offering hope for restoring damaged organs and treating degenerative conditions
