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Expanding numbers of blood stem cells prior to therapeutic transplantation

Two recent studies highlight potential strategies to expand blood (hematopoietic) stem cells in vitro (in a laboratory dish) in order to generate more of these rare cells prior to therapeutic transplantation in people. Hematopoietic stem cell (HSC) transplants can be life-saving for people with a number of conditions. When introduced into a donor, HSCs migrate to the bone marrow where they normally reside and renew—and when needed mature into all types of blood cells (e.g., red cells, white cells, and platelets). However, it can be challenging to find HSCs in needed quantities from a donor whose cells are similar enough to a patient’s cells to be a sufficient “match” for transplantation. Researchers supported by NIDDK continue studies to discover key factors that promote HSC expansion in vitro, and with these insights increase the potential availability of transplantation to benefit many more people.

In the search for ways to promote expansion of HSCs, one team of scientists focused on a protein called DEK. Previous research has shown that DEK is an abundant protein found in most human tissues, and that it may regulate blood cell development. In a recent study, the researchers found that a synthetically produced secreted form of the DEK protein was shown to greatly enhance expansion of mouse (both male and female) and human HSCs within 4 days in vitro. This finding is important as the ability to transplant increased numbers of HSCs might improve transplantation outcomes in the recipient.

Another research team sought to optimize the components of the liquid culture medium in which HSCs are expanded in vitro, and the surface that they are grown on. For example, serum albumin has long been used as part of the culture medium for the expansion of HSCs, but it contains a complex mixture of proteins, often inadequately characterized. In a recent study in mice, the researchers described the development of a defined culture system that includes a component called “polyvinyl alcohol” (PVA) as a substitute for serum albumin, and optimized levels of two other components, thrombopoietin and stem cell factor. They also used another factor, fibronectin, to coat the dish on which the cells are expanded. The researchers found that this culture system supports long-term expansion of mouse HSCs. Both male and female mice were used in this study. This culture system facilitated expansion of HSCs between 236-fold and 899-fold during a 1-month timeframe. Furthermore, when transplanted into recipient mice, the expanded HSCs migrated to and engrafted into the bone marrow without the mice having to undergo standard, but toxic, pre-conditioning regimens.

Taken together, these research studies highlight potential new strategies to expand transplantable HSCs ex vivo prior to therapeutic transplantation. Future research could determine whether these strategies improve HSC transplantation in people.

Capitano ML, Mor-Vaknin N, Saha AK,…Broxmeyer HE. Secreted nuclear protein DEK regulates hematopoiesis through CXCR2 signaling. J Clin Invest 129: 2555-2570, 2019.

Wilkinson AC, Ishida R, Kikuchi M,…Yamazaki S. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature 571: 117-121, 2019.

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