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Extracellular Vesicles Boost Grafting Ability in Cells

Aug 20, 2019 10:11:00 AM / by Stacy Matthews Branch, DVM, PhD

Young woman with PCR props in genetics laboratory_AdobeStock_199001796-1A new study shows that we may be able to boost the grafting ability in cells for people receiving a bone marrow transplant.

Allogenic stem cell transplantation is a treatment approach in people with diseases that are destructive to the bone marrow, such as multiple myeloma, leukemia, and Hodgkin´s lymphoma. The goal is to restore bone marrow after total-body chemotherapy and irradiation. The transplantation procedure involves transferring hematopoietic stem cells from compatible, healthy donors to a patient. An important complication of this procedure is rejection and destruction of the donated stem cells by the recipient’s immune system before engraftment can occur.

The likelihood of engraftment success has been increased with the administration of mesenchymal stromal cells (MSCs). MSCs from the bone marrow (and certain other tissues) are multipotent stromal cells that have the capacity to differentiate into other cell types. Previous studies in lab animals have shown that administering MSCs during transplantation increases engraftment and blood cell function. Further, these favorable effects of MSCs have been found to occur via the release of extracellular vesicles from MSCs. These findings have led a group of scientists to examine the changes that can be induced in CD34 stem cells after infusing them with MSC-derived extracellular vesicles.

CD34 stem cells (from leukapheresis products) and bone-marrow MSCs were isolated from healthy human donors. Extracellular vesicles were isolated from MSCs and cultured with the human CD34 stem cells to allow incorporation of the vesicles into the cells, while CD34 stem cells without vesicles served as controls. Experimental mice received total body irradiation six hours before hematopoietic stem cell transplantation. The femurs of anesthetized mice were transplanted with CD34 stem cells with or without MSC-derived extracellular vesicles, then engraftment of the cells was evaluated 4 weeks later.

The clonogenic capacity of the vesicle-containing CD34 stem cells was increased (as measured by progenitor cell GFU-GM), and they had higher viability. There was significant donor chimerism (reflecting stem cell engraftment) in the femurs injected with CD34 stem cells with extracellular vesicles when compared to those containing non-vesicle stem cells. This data demonstrates that CD34 stem cells incorporating human MSC‐derived extracellular vesicles can increase bone marrow lodging ability in vivo. This approach may be valuable for increasing engraftment success in patients receiving bone marrow transplants.

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Reference: Preciado, S., Muntión, S., Corchete, L., Ramos, T., de la Torre, A., & Osugui, L. et al. (2019). The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability. STEM CELLS. doi:10.1002/stem.3032

Topics: Bone Marrow, Stem Cells, Blood Disorders

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