Title:Strategies to Protect Hematopoietic Stem Cells from Culture-induced Stress Conditions
Volume: 16
Issue: 7
Author(s): Fatima Aerts-Kaya*
Affiliation:
- Department of Stem Cell Sciences, Graduate School of Health Sciences, Hacettepe University, Ankara,Turkey
Keywords:
Hematopoietic stem cells, oxidative stress, endoplasmic reticulum stress, replicative stress, hematopoietic stress,
cellular stress.
Abstract:
In contrast to their almost unlimited potential for expansion in vivo and despite years of
dedicated research and optimization of expansion protocols, the expansion of hematopoietic stem cells
(HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved
in maintenance, expansion and differentiation of HSCs will enable the development of better
protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment
potential and a better understanding of the effects of the external influences in and on the hematopoietic
niche that may affect HSC function.
During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce
different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment
potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen
shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to
DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on
HSC potential, provide a better understanding of the true impact of certain treatments in the absence of
confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of
HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence
or loss of cell viability. This review summarizes some of the available strategies that may be
used to protect HSCs from culture-induced stress conditions.
