Protection of hematopoietic stem cells from stress-induced exhaustion and aging

Purpose of review Hematopoietic stem cells (HSCs) are defined by their ability to self-renew and differentiate to replenish all blood lineages throughout adult life. Under homeostasis, the majority of HSCs are quiescent, and few stem cells are cycling to sustain hematopoiesis. However, HSCs can be induced to proliferate and differentiate in response to stress signals produced during infection, inflammation, chemotherapy, radiation, bone marrow transplantation, and aging. Recent evidence suggests that acute and chronic stress impact the number and function of HSCs including their ability to repopulate and produce mature cells. This review will focus on how chronic stress affects HSC biology and methods to mitigate HSC loss during chronic hematopoietic stress. Recent findings Quiescent HSCs exit dormancy, divide, and differentiate to maintain steady-state hematopoiesis. Under conditions of acute stress including infection or blood loss some HSCs are pushed into division by cytokines and proinflammatory stimuli to differentiate and provide needed myeloid and erythroid cells to protect and reconstitute the host; after which, hematopoiesis returns to steady-state with minimal loss of HSC function. However, under conditions of chronic stress including serial bone marrow transplantation (BMT), chronic inflammation, and genotoxic stress (chemotherapy) and aging, HSCs are continuously induced to proliferate and undergo accelerated exhaustion. Recent evidence demonstrates that abl...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. Capitano Source Type: research