Blood stem cells, which are crucial for life-saving treatments for blood cancers and immune disorders, have the ability to renew themselves. However, this ability diminishes when the cells are placed in a lab environment. Researchers have discovered a protein that not only allows blood stem cells to self-renew in a lab setting but also helps these expanded cells to effectively function after being transplanted into mice. These findings have the potential to increase the availability of blood stem cell transplants and enhance the safety and accessibility of gene therapies using these cells. UCLA scientists have made this discovery.Researchers have discovered a protein that is crucial in controlling the self-renewal of human blood stem cells by aiding them in detecting and understanding signals from their surroundings. The findings, which were published in Nature, bring scientists closer to developing techniques for expanding blood stem cells in a lab environment. This could potentially make life-saving transplants of these cells more accessible and improve the safety of blood stem cell-based treatments, including gene therapies. Hematopoietic stem cells, also called blood stem cells, are capable of replicating themselves through self-renewal and can specialize into various types of blood cells.Blood stem cells are essential for producing all the blood and immune cells in the body. They have been used for many years in transplants to treat blood cancers like leukemia and other blood and immune disorders.
However, there are drawbacks to blood stem cell transplants. It can be challenging to find a compatible donor, especially for those of non-European backgrounds. Additionally, there may not be enough stem cells available for a safe and effective transplant.
These limitations exist because once blood stem cells are removed from the body and placed in a lab dish, they quickly lose their ability.The challenge to creating fully functional blood stem cells is understanding what causes them to not work properly when transplanted, even though they have all the characteristics of authentic blood stem cells. Dr. Hanna Mikkola, a senior author of a new study at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, stated that while scientists have been able to produce cells that closely resemble blood stem cells, there is still a crucial element missing. In order to identify this missing component, Julia Aguade Gorgorio, the first author of the study, conducted research.The main author examined sequencing data to detect the genes that become inactive when blood stem cells are placed in a laboratory dish. MYCT1, a gene that produces a protein of the same name, was identified as crucial to the cells’ ability to renew themselves.
The researchers discovered that MYCT1 regulates endocytosis, a process that is important in how blood stem cells absorb signals from their surroundings that instruct them on self-renewal, differentiation, and quiescence.
“When cells receive a signal, they must internalize and process it; MYCT1 controls the speed and efficiency of this process.”adequate information to make decisions and navigate their environment efficiently. The researchers believe that understanding the role of MYCT1 in blood stem cells could have significant implications for the development of new treatments for conditions such as leukemia, where the dysregulation of stem cells is a key factor.The researchers then utilized a viral vector to reintroduce MYCT1 in order to assess whether its presence could reestablish the ability of blood stem cells to renew themselves in a laboratory environment. Their findings showed that reintroducing MYCT1 not only reduced the stress on the blood stem cells and enabled them to renew themselves in culture, but also allowed these expanded cells to effectively perform their functions after being transplanted into mouse models.
Moving forward, the team will focus on investigating the reasons behind the silencing of the MYCT1 gene and exploring ways to prevent this silencing without the need for a viral vector, which would be a safer approach for clinical applications.
The lead researcher stated, “If we can find a way to maintain MYCT1 expression in blood stem cells, it could potentially lead to improved treatments for a variety of blood-related disorders.”Mikkola, a professor of molecular, cell and developmental biology in the UCLA College and a member of the UCLA Health Jonsson Comprehensive Cancer Center, stated that if MYCT1 expression in blood stem cells can be maintained in culture and after transplant, it will pave the way for maximizing other advances in the field. This would not only make blood stem cell transplants more accessible and effective but also improve the safety and affordability of gene therapies that use these cells. The research was supported by the National Institutes of Health, the Swiss National Science Foundation, the European Molecular Biology Organization.The study was funded by a variety of organizations including the UCLA Jonsson Cancer Center Foundation, the James B. Pendleton Charitable Trust, the McCarthy Family Foundation, the California Institute for Regenerative Medicine, the UCLA AIDS Institute, the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center, the Royal Society, the Wellcome Trust, and the UCLA Broad Stem Cell Research Center Stem Cell Training Program.
