A new collaboration between American and Chinese researchers may soon help to solve the central problem with embryonic stem cell medicine: the high risk of rejection of donor cells by the body’s immune system.
As an ancillary benefit, lead investigator Yang Xu, of the University of California at San Diego, says the team’s findings may also help science better understand how tumors beat the immune system as they spread throughout the body.
In the study, investigators designed “humanized” laboratory mice with a functional human immune system capable of rejecting a large number of foreign cells originated from human embryonic stem cells -- just like the real thing. The “allogeneic” nature of the human embryonic stem cell, so different from cells of the body, means any healthy immune system would normally attack the invasive cells.
Yet, Xu and his colleagues say the body’s allogeneic immune response may be lowered by immunosuppressant drugs, which have proven successful for recipients of donor organ transplantations. However, the drug class does not provide a complete solution for the problem.
"[F]or stem cell therapies, the long term use of toxic immunosuppressant drugs for patients who are being treated for chronic diseases like Parkinson's disease or diabetes pose serious health problems," Xu said in a statement.
In the study, the investigators prodded the “humanized” immune response in the laboratory mice with various immune-suppressing molecules, finding that a combination of molecules --dubbed CTLA4-lg -- protected invasive cells from immune response. The molecular combination was produced by mixing a drug used to treat rheumatoid arthritis with PD-L1, a protein that allows tumors to evade an immune response in the body.
"If we express both molecules in cells derived from human embryonic cells, we can protect these cells from the allogeneic immune rejection,” Xu said.”If you have only one such molecule expressed, there is absolutely no impact. We still don't know exactly how these pathways work together to suppress immune rejection, but now we've got an ideal system to study this."
Presently, patients hoping to benefit from embryonic stem cell transplantation must choose between a lifelong use of immunosuppressant drugs or living with the symptoms of their disease -- an unfortunate choice researchers hope to soon eliminate. The research was published in the journal Stem Cells.