Stem cell transplant recipients demystify the fate of donated stem cells Premium

Long-term study on stem cell transplants reveals low mutation rates in donors and recipients, supporting bone marrow regeneration.

A new human study involving some of the longest-living survivors of hematopoietic stem cell transplants sheds light on how transplanted stem cells from donors change after engraftment and mutate over time. The results were published in the journal Science Translational Medicine.

The findings, gathered from a unique group of 16 pairs of donors and recipients, suggest that the rate of mutations and clonal expansion stayed fairly similar and surprisingly low between donors and recipients for as long as 46 years after transplant. “Our data set the foundation for studying clinically relevant questions, such as the impact of donor age and preexisting donor CH [clonal hematopoiesis] on the long-term outcomes of [transplant] recipients,” the authors write.

Hematopoietic stem cell transplants are life-saving procedures for people with blood cancers. After receiving a transplant, it is up to the donated stem cells to rebuild the recipient’s entire blood cell-forming (or hematopoietic) machinery. This subjects the donor cells to a fair amount of replicative stress. Some scientists are concerned that this stress could lead to clonal hematopoiesis, a phenomenon where the donated stem cells acquire mutations that might one day lead to cancer or chronic diseases.

The researchers obtained and analysed blood samples from 16 pairs of stem cell donors and recipients, at a median time of 33.6 years after transplant. They performed whole genome sequencing with a technique called duplex sequencing, focusing on many genes that tend to be mutated in myeloid cancers and clonal hematopoiesis. This revealed that all the donors had some degree of clonal hematopoiesis variants, even in their earliest blood samples. However, the average rate of mutations in these genes was similar in donors compared to the recipients (2% vs. 2.6% per year).

This led the authors to conclude that there does not appear to be any widespread clonal expansion in stem cells even decades after transplant, a finding they say supports the immense regenerative capabilities of bone marrow.