Journal
STEM CELLS AND DEVELOPMENT
Volume 27, Issue 19, Pages 1303-1321Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2017.0291
Keywords
atmospheric oxygen; dissolved oxygen; human mesenchymal stem cell; hypoxia; mammalian tissue culture; normoxia
Funding
- Engineering and Physical Research Council, United Kingdom [EP/L015072/1]
- School of Sport, Exercise and Health Sciences, Loughborough University
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Most cells in the human body, including human mesenchymal stem cells (hMSCs), have evolved to survive and function in a low physiological oxygen (O-2) environment. Investigators have become increasingly aware of the effects of O-2 levels on hMSC biology and culture and are mimicking the natural niche of these cells in vitro to improve cell culture yields. This presents many challenges in relation to hMSC identity and function and in the maintenance of a controlled O-2 environment for cell culture. The aim of this review was to discuss an hMSC checklist as a guide to establishing which identity and potency assays to implement when studying hMSCs. The checklist includes markers, differentiation potential, proliferation and growth, attachment and migration, genomic stability, and paracrine activity. Evidence drawn from the current literature demonstrates that low O-2 environments could improve most hMSC checklist attributes. However, there are substantial inconsistencies around both the terminology and the equipment used in low O-2 studies. Therefore, hypoxia as a term and as a culture condition is discussed. The biology of short-term (acute) versus long-term (chronic) hypoxia is considered, and a nascent hypothesis to explain the behavior of hMSCs in long-term hypoxia is presented. It is hoped that by establishing an ongoing discourse and driving toward a regulatory recognizable hMSC checklist, we may be better able to provide the patient population with safe and efficacious regenerative treatments.
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