Blood study tracks what happens to stem cells decades after transplant

A new study on the long-term dynamics of transplanted stem cells within a patient's body explains how age affects stem cell survival and immune diversity, an insight that could make transplants safer and more successful. We provide.

For the first time, scientists have tracked what happens to stem cells decades after a transplant, uncovering a procedure that has been a medical mystery for more than 50 years. Insights may pave the way for new strategies in donor selection and transplant success, leading to safer and more effective transplants.

Researchers at the Wellcome Sanger Institute and colleagues at the University of Zurich have successfully mapped the behavior of stem cells in a recipient's body for up to 30 years after transplant, providing the first glimpse into the long-term dynamics of these cells. I was able to do that. .

the study, published October 30th naturerevealed that transplants from older donors often have lower success rates, with one-tenth the number of vital stem cells surviving the transplant process. Some of the surviving cells also lose the ability to produce a variety of blood cells, which are essential for a strong immune system.

Each year, more than 1 million people worldwide are diagnosed with blood cancers, which include cancers such as leukemia and lymphoma, which can cause a person's immune system to malfunction. there is. Stem cell transplants, also known as bone marrow transplants, are often the only curative treatment option for patients.

This procedure replaces the patient's damaged blood cells with healthy stem cells from a donor, rebuilding the patient's entire blood and immune system. In the UK alone, more than 2,000 people undergo this procedure every year.

Despite being practiced for over 50 years, many fundamental questions about how transplants work remain unanswered. Although potentially lifesaving, outcomes vary widely and many patients end up facing complications years later. Although donor age is known to affect success rates, what happens at the cellular level after transplantation has until now been a “black box”.

In this new study, researchers at the Wellcome Sanger Institute and the University of Zurich used advanced genomic sequencing techniques to examine blood samples from 10 donor-recipient sibling pairs up to 31 years after transplantation. Analyzed.

By analyzing the mutations that occur in donor and recipient stem cells throughout their lives, researchers can now track how many stem cells survive the transplant process and continue to produce new blood cells in the patient's body. This is an approach that has not been possible before.

The researchers found that transplants from younger donors in their 20s and 30s had about 30,000 long-term survival stem cells, compared to just 1 to 3,000 from older donors. This decline may lead to decreased immunity and increased risk of recurrence, and may explain why younger donors often have better outcomes.

They also found that the transplant process aged the recipient's blood system by about 10 to 15 years compared to the matched donor, primarily due to lower stem cell diversity.

Surprisingly, despite the intense stress of the transplant process, few new genetic mutations occur because stem cells divide rapidly to rebuild the patient's blood. This calls into question previous assumptions about high mutation rates during transplantation.

The study also identified other genetic factors that help certain stem cells proliferate after transplantation, regardless of donor age. Such a wide range of genetic advantages could lead to the development of better treatments, making transplantation safer and more effective for a wider range of patients.

Dr. Michael Spencer-Chapman, lead author of the study from the Wellcome Sanger Institute, said: “Receiving a transplant is like giving your blood system a new start, but what actually happens to those stem cells is unknown. So far, all we have to do is introduce cells and monitor blood cell counts for signs of recovery.

“However, this study tracks changes over decades in a single sample, and how some cell populations decline and others predominate, and how patients' blood changes over time. It's interesting to understand this process in such detail.”

Dr. Markus Manz, senior author of the study from the University of Zurich, said: “This study highlights that age is not just a number, but an important factor for transplant success. The hematopoietic stem cell system Although surprisingly stable, younger donors typically provide a broader and more diverse range of stem cells, which may be important for a patient's long-term recovery.

“We continue to explore other factors that influence long-term hematopoietic stem cell dynamics to fine-tune both donor selection and recipient bone marrow environment to achieve optimal long-term stem cell function. I am thinking of doing so.”

“The transplant process involves blood and immune cells passing through a kind of genetic 'bottleneck',” said Dr Peter Campbell, senior author of the study at the Wellcome Sanger Institute. Our new approach allows us to investigate this bottleneck phenomenon in more detail.

“We found that the bottleneck provides multiple different opportunities for some stem cells to proliferate in the recipient's new environment than others. We believe it is possible to discover a gene that allows us to reproduce better than others, and then, in theory, we could use the gene to increase the success rate of transplant surgeries. .”