Stem cells from young donors more diverse and longer lasting

Blood stem cell transplants are most successful when the donor is younger, according to a long-term study following transplant recipients and their donors decades after surgery.

Allogeneic haematopoietic stem cell transplant – more commonly known as a bone marrow transplant – involves replacing the patient's blood stem cells with those of a matched sibling donor. Before treatment, the patient has their old stem cells destroyed, typically using chemotherapy or radiotherapy. They then receive the new stem cells via an intravenous infusion to re-establish healthy blood cell production. Now, scientists from the Wellcome Sanger Institute, near Cambridge and the University of Zurich, Switzerland, have analysed what happens to the stem cells, in both the recipient and donor, decades after a transplant.

'When you receive a transplant, it's like giving your blood system a fresh start, but what actually happens to those stem cells? Until now, we could only introduce the cells and then just monitor the blood counts for signs of recovery,' said Dr Michael Chapman, first author of the study at the Wellcome Sanger Institute. 'But in this study we've traced decades of changes in one single sample, revealing how some cell populations fall away while others dominate, shaping a patient's blood over time.'

Publishing their results in Nature, the scientists analysed blood samples taken from ten patients and their matched sibling donor between nine and 31 years post-transplant. All patients had undergone haematopoietic stem cell transplants.

Using advanced genomic sequencing techniques, they discovered that the stem cells from younger donors (18–47 years at transplant) were tenfold higher in their respective recipient compared to stem cells from older donors (50–66 years). The transplanted stem cells were still producing new blood cells in the recipients at the time of analysis. The authors hypothesise that the lower level of stem cells that survived the transplant from older donors could explain why haematopoietic stem cell transplants from younger donors often result in better outcomes.

'This study reveals a fascinating level of detail about what happens to cells in the years and decades after a stem cell transplant,' said Dr Tania Dexter from Anthony Nolan, a UK charity connecting stem cell donors with patients. 'The findings support [our] research which shows the age of the donor makes a difference, and reinforce the decision to lower the recruitment age of our register to 16 to help make sure more patients in need of an unrelated donor have the best possible transplant. Studies like these are vital to continue to improve transplants and ensure more patients can survive and thrive in future.'

Furthermore, the scientists found that the diversity of the recipients' blood cells was less than their donors, which the authors claim ages the blood system in recipients by about ten to 15 years.

The scientists also found that stem cells do not gain many new genetic mutations during the transplant process, even though the cells rapidly divide to rebuild the patient's blood.

Genetic factors were also discovered that help certain stem cells thrive following transplant, which the scientists hope could lead to the development of safer and more effective treatments.

An allogeneic haematopoietic stem cell transplant attempts to cure a serious illness such as thalassemia, sickle cell disease or leukaemia (see BioNews 1218, 1112 and 1088).