Advancing Stem Cell Transplants
Transplantation, a critical medical procedure, often faces challenges due to donor shortages and immune rejection. In 2021, 6,000 individuals in the U.S. passed away while waiting for a transplant, as reported by donatelife.net. Stem cell-derived transplants hold promise for addressing this shortage, but they too face hurdles, notably the risk of immune rejection.
The Challenge of Immune Rejection
When transplanting cells or tissues, whether from living or deceased donors, matching the donor material with the recipient’s immune system is crucial to avoid rejection. Stem cell research aims to address this through hypoimmunogenic stem cells. These cells are genetically altered to evade immune detection, creating a universal stock for transplants without the need for immune matching. However, this poses another risk: the unchecked growth and tumor formation from immature cells within the transplant.
A Dual Strategy for Safe Transplantation
In a significant development, researchers led by Baoyang Hu from the Chinese Academy of Sciences, Beijing, have engineered a solution. They modified stem cells to produce liver cells that are immune-resistant while ensuring that immature, potentially cancerous stem cells remain vulnerable to the immune system. This was achieved by programming the cells to express two immunosuppressive proteins upon maturation into liver cells. Immature stem cells do not produce these proteins, making them targets for immune elimination.
When these engineered stem cells were transplanted into mice with a human immune system, the immature stem cells were destroyed, preventing tumor formation. Simultaneously, the mature liver cells evaded immune attack, demonstrating the potential of this approach.
Implications and Future Directions
This technique opens avenues for protecting various stem cell-derived tissues, such as heart and pancreatic cells, from immune rejection. The findings, published in Stem Cell Reports, represent a significant step forward, though further pre-clinical and clinical validations are necessary to confirm the safety and efficacy of these stem cell-derived transplants.