Stem Cell Transplant 'Black Box' Unveiled in 31-Year Study of Blood Cells
A pioneering study has provided the first detailed insight into the long-term behavior of stem cells following transplants, offering new hope for improving the procedure that has remained largely unexplained for more than 50 years.
Researchers from the Wellcome Sanger Institute, in collaboration with the University of Zurich, have traced the dynamics of transplanted stem cells in patients' bodies for up to 30 years, significantly advancing our understanding of how these cells survive and function over time.
Published in Nature and supported in part by Cancer Research UK, the study reveals how stem cells behave after being transferred from donor to recipient. One of the key findings is that transplants from older donors, which tend to be less successful, have significantly fewer stem cells that survive long-term. Older donor cells are also less capable of generating the wide range of blood cells necessary for a strong immune system, which could explain the poorer outcomes observed in older donor transplants.
Stem cell transplants, or bone marrow transplants, are a critical treatment for blood cancers like leukemia and lymphoma, which affect millions of people globally. The procedure involves replacing damaged blood cells in patients with healthy stem cells from a donor, rebuilding the patient's blood and immune system. However, the long-term outcomes of these transplants have varied, with many patients experiencing complications years after the procedure. While donor age has long been known to affect success rates, the exact cellular mechanisms have remained unknown—until now.
In this study, scientists used advanced genome sequencing to analyze blood samples from ten donor-recipient sibling pairs, allowing them to track the behavior of stem cells decades after the transplant. By examining mutations accumulated over the lifespan of the donor and recipient cells, the team reconstructed the evolution of the transplanted cells, showing how many stem cells survived and how they adapted to the recipient’s body.
The research found that transplants from younger donors—typically those in their 20s or 30s—resulted in around 30,000 stem cells surviving long-term, while older donors had only 1,000 to 3,000 surviving stem cells. The study suggests that this reduction in surviving stem cells in older donors may lead to weaker immune systems and a higher risk of disease relapse in recipients.
One surprising outcome of the study was the finding that the transplant process itself accelerates the aging of the recipient’s blood system by 10-15 years compared to the donor. This effect is primarily due to a decrease in stem cell diversity in the recipient after the transplant. Additionally, the researchers discovered that stem cells accumulate fewer new genetic mutations during the transplant process than previously thought, despite the high levels of cell division involved in rebuilding the patient’s blood system.
The research also points to genetic factors that influence how well certain stem cells thrive after the transplant, regardless of the donor's age. These insights could lead to new ways to optimize donor selection and improve transplant outcomes by identifying and leveraging genetic traits that enhance stem cell survival and function.
Dr. Michael Spencer Chapman of the Wellcome Sanger Institute, the study’s lead author, emphasized the significance of the findings, stating:
“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. 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. It is exciting to understand this process in such detail.”
Senior author Dr. Markus Manz from the University of Zurich added that donor age plays a crucial role in long-term recovery:
“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 hematopoietic 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.”
The study was published in Nature under the title "Clonal dynamics after allogeneic haematopoietic cell transplantation using genome-wide somatic mutations", DOI: 10.1038/s41586-024-08128-y
Image credit: luismmolina
Topics: Biotech
