Journal
CURRENT OPINION IN HEMATOLOGY
Volume 24, Issue 4, Pages 314-321Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000347
Keywords
bone marrow reconstituting niche; bone marrow transplantation; hematopoietic stem cells; oxidative stress
Categories
Funding
- American Society of Hematology
- Hartwell Foundation
- NIDDK [K01DK080846, R01DK104028]
- American Lebanese Syrian Associated Charities
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Purpose of reviewHematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation.Recent findingsDuring transplantation, HSCs encounter a damaged bone marrow niche, characterized molecularly by increases in oxygen concentrations and an altered cytokine milieu. New mechanisms and pathways have been recently implicated during HSCT, including transplanted HSC-dependent secretion of conditioning molecules that facilitate engraftment and pathways that protect HSCs from perturbed organelle homeostasis.SummaryBetter understanding the molecular processes HSCs employ to withstand the stress of transplant will illuminate novel targets for further improving conditioning regimens and engraftment during HSCT.
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