A major research project has “lifted the lid” on what happens to stem cells in the decades following a transplant.
The most significant finding of the project, led by the Wellcome Trust Sanger Institute in Cambridge, UK, was that cells from youthful donors are by far the most long-lasting, helping explain why donor age is a key factor in the success of transplants.
Reporting in Nature, the researchers say that about 30,000 stem cells survive long-term when they come from donors in their 20s and 30s. Fewer than 3,000 cells survived from older donors.
The study also found that the blood system of recipients “ages” much faster than that of their donors – with a gap of around 10 to 15 years emerging. This is mainly because of reduced stem cell diversity.
The study, conducted in collaboration with the University of Zurich in Switzerland, involved the whole genome sequencing of cells from ten donor-recipient pairs of siblings, up to 31 years after transplant.
Another finding was that stem cells suffer few genetic mutations after transplant, in spite of their rapid division to rebuild the recipient’s blood supply.
Dr Michael Spencer Chapman, from the Wellcome Sanger Institute, said: “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. It is exciting to understand this process in such detail.”
Study co-leader Dr Peter Campbell said: “The transplant process forces blood and immune cells through a type of genetic ‘bottleneck’. Our new approach allows us to investigate this bottleneck phenomenon more closely. We find that the bottleneck provides multiple different opportunities for some stem cells to thrive more than others in their new environment in the recipient. We believe it will be possible to find the genes responsible for enabling some stem cells to thrive better than others – these genes could then in theory be harnessed to improve the success of the transplant procedure.”
The other study co-leader Dr Markus Manz, from University of Zurich, said: “The research highlights that age is more than just a number — it’s an important factor in transplant success. Although the hematopoietic stem cell system is amazingly stable over time, younger donors generally supply a larger and more diverse range of stem cells, which might be crucial for patients’ long-term recovery. We hope to continue exploring other factors that affect long-term haematopoietic stem cell dynamics in order to fine-tune both donor selection as well as recipient bone-marrow environments for optimal long-term stem cell function.”
Source:
Spencer Chapman M, Wilk CM, Boettcher S, Mitchell E, Dawson K, Williams N, Müller J, Kovtonyuk L, Jung H, Caiado F, Roberts K, O'Neill L, Kent DG, Green AR, Nangalia J, Manz MG, Campbell PJ. (2024) “Clonal dynamics after allogeneic haematopoietic cell transplantation using genome-wide somatic mutations.” Nature, 30 October 2024, doi: 10.1038/s41586-024-08128-y.
Link: https://www.nature.com/articles/s41586-024-08128-y
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