Blood research reveals the 'black box' of stem cell transplants

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. .

This study was announced today (October 30th). nature The study, part-funded by Cancer Research UK, revealed that transplants from older donors often have poor success rates, with one in ten fewer 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.

More than 1 million people worldwide are diagnosed with blood cancer each year¹including cancers such as leukemia and lymphoma, and can stop a person's immune system from functioning properly. 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, over 2,000 people undergo this procedure every year².

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. Donor age is known to influence success rate³but 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 genome sequencing technology to analyze blood samples from 10 donor-recipient sibling pairs up to 31 years after transplantation. did.⁴.

By analyzing the mutations that occur in donor and recipient stem cells throughout their lives, scientists 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 never 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.⁵. 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 Wellcome Sanger Institute study, said: “Receiving a transplant is like giving your blood system a new start, but what actually goes into those stem cells? Will it happen? So far, but , this study tracks changes over decades in a single sample, revealing how some cell populations decline and others predominate, shaping a patient's blood over time. It's great to be able 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 is surprisingly stable, although younger donors generally have a wider range of We are providing a more diverse range of stem cells, which may be important for a patient's long-term recovery, and are encouraging the exploration of other factors that influence long-term hematopoietic stem cell dynamics to fine-tune both. We hope to continue: donor selection and recipient bone marrow environment for optimal long-term stem cell function.”

Dr Peter Campbell, senior author of the study from the Wellcome Sanger Institute, said: “The transplant process involves blood and immune cells passing through a kind of genetic 'bottleneck'. Our new approach , we will be able to investigate this bottleneck phenomenon in more detail. The neck allows some stem cells to proliferate better than others because they provide multiple different opportunities for some stem cells to proliferate in the recipient's new environment than others. We believe that it is possible to find a gene that can be used to increase the success rate of transplant surgery.”

1. https://www.worldwidecancerresearch.org/information-and-impact/cancer-myths-and-questions/what-is-blood-cancer-and-why-do-we-need-more-research/#:~: text=Blood%20Cancer%20 is %205th of %20, diagnosed with %20%20Worldwide%20in%202020
2. https://www.blood.co.uk/news-and-campaigns/news-and-statements/nhsbt-celebrates-stem-cell-donors-and-transplants/
3. https://www.anthonynolan.org/blog/2018/02/23/research-shows-donor-age-most- important-in-stem-cell-transplant-survival
4. In this study, the donor is considered a “control.” By comparing genetic changes in both donor and recipient blood samples through whole-genome sequencing, the researchers reconstructed their evolutionary history and understood how the cells adapted and changed after transplantation. These samples were taken between 9 and 31 years post-transplant.
5. Some stem cells had advantages before transplantation, allowing them to better adapt to their new environment within the recipient's body. These include increased survival rates during harvest or preparation, while others have gained an advantage after transplantation due to genetic mutations that allow them to proliferate within the recipient's bone marrow. Understanding these patterns could help doctors improve the transplant process and better select stem cells with a higher chance of success, regardless of donor age.