Donor age is a crucial factor for the long-term success of stem cell transplantation.

For the first time, researchers have tracked what happens to stem cells decades after transplantation, shedding light on a procedure that has remained a mystery for over 50 years. The findings could pave the way for new strategies in donor selection and successful transplantation, potentially leading to safer and more effective transplants.

Scientists from the Wellcome Sanger Institute and their colleagues from the University of Zurich were able to create a picture of stem cell behavior in the bodies of recipients over a span of three decades after transplantation, gaining insights into the long-term dynamics of these cells.

The study, published on October 30 in the journal Nature, reveals that when transplants are performed from older donors, which are often less successful, ten times fewer vital stem cells survive. Some of the surviving cells also lose the ability to produce a range of blood cells essential for a strong immune system.

While transplantation can save lives, its outcomes vary significantly, and many patients face complications many years later. It is known that the donor's age affects success rates, but what happens at the cellular level post-transplantation has remained a "black box."

In this new study, scientists utilized advanced genome sequencing methods to analyze blood samples from ten pairs of donors and recipients (who were siblings) over a period of 31 years following transplantation.

By examining the mutations occurring throughout life in the stem cells of both donors and recipients, they were able to track how many stem cells survived the transplantation process and continued to produce new blood cells in the patient’s body, which was previously impossible.

The team found that with transplants from young donors (aged 20-30 years), approximately 30,000 stem cells survive over the long term, while in the case of older donors, this number drops to only 1-3,000. This decrease in survival may lead to reduced immunity and an increased risk of relapse, which may explain why transplants from younger donors often yield better results.

Researchers also discovered that the transplantation process ages the recipients' circulatory systems by about 10-15 years compared to matched donors, primarily due to a lower diversity of stem cells.

Dr. Michael Spencer Chapman, a study author from the Wellcome Sanger Institute, stated: “When a person undergoes a transplant, it's as if they are starting their blood system from scratch, but what actually happens to these stem cells? Until now, we could only introduce cells and then monitor blood indicators for signs of recovery. But in this study, we traced decades of changes in a single sample, showing how some cell populations disappear while others dominate, shaping the patient’s blood over time. It was fascinating to understand this process in such detail.”

The research underscores that age is not just a number but a crucial factor in transplantation success. While the hematopoietic stem cell system is remarkably stable over time, young donors typically provide a larger and more diverse set of stem cells, which can be critical for patients' long-term recovery.