Mitochondrial DNA mutations may help account for rejection of stem cell transplants

Scientists have viewed transplantation of so-called induced pluripotent stem cells (iPSCs), which can be reprogrammed into virtually any tissue or organ in the body, as a key event in the regenerative medicine revolution. But their surprising tendency to get rejected by the body in preclinical studies has led to setbacks.

Now, a group of researchers is reporting a possible reason why. In studies using mice, they discovered that mutations in mitochondrial DNA can trigger an immune response that could lead to rejection of stem cell transplants. Using immune cells from actual organ transplant recipients, the researchers also showed that a similar rejection process involving mitochondrial DNA can occur in humans and may be involved in organ transplant rejection, they suggest.

Study co-author Hannah Valantine, M.D., whose lab performed the genetic sequencing to identify the mitochondrial DNA mutations, said that the findings could have a significant impact on the field of transplantation. “This study uncovers a possible new mechanism by which transplants are rejected, and which might be leveraged in the future to develop better diagnostic and immunosuppressive agents.” Valantine is lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at the NHLBI.

The study, funded in part by NHLBI, appeared in the journal Nature Biotechnology.

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University of California San Francisco news release