Abstract
Mesenchymal stem cells (MSC) are considered non-hematopoietic multipotent stem cells with self-renewal properties and the ability to differentiate into a variety of mesenchymal tissues. Optimal conditions for the culture of these cells have been the subject of investigation for several years. In particular, ideal oxygen tension levels have not been established in the literature. In physiological environments, oxygen tension may vary from 12% in peripheral blood to 1% in the deep zone of cartilage regions. In any case, oxygen tension is considerably lower in vivo when compared with the normal atmosphere of standard cell culture conditions (21%). The objective of this study was to review the literature available on MSC characteristics (cell cycle, survival, proliferation, differentiation, morphology, immunophenotype, cytogenetics) when cultured under hypoxic conditions. Our focus on optimal culture conditions is justified by the key role currently played by these cells in regenerative medicine.
Highlights
Mesenchymal stem cells (MSCs), referred to mesenchymal stromal cells [1], are considered non-hematopoietic multipotent stem cells with self-renewal properties and the ability to differentiate into mesoderm tissues [2]
The first studies designed to assess the effects of different oxygen (O2) tension levels in MSC culture date back to 1958, when Cooper et al and Zwartouw & Westwood observed that some cells proliferated more rapidly under low O2 tension levels when compared with normal atmospheric levels [7,8]
Studies have evidenced that MSC are recruited to areas of tissue damage, such as fractures, myocardial infarction, and ischemic brain lesions, where they become involved in both the regulation of inflammatory response and tissue repair [9,10], and hypoxia appears to be an important regulator of MSC recruitment, migration, and differentiation [11,12], In an animal model, Rochefort et al have shown that MSCs, but not hematopoietic progenitor cells, were mobilized from the bone marrow into peripheral blood through hypoxia [13]
Summary
Mesenchymal stem cells (MSCs), referred to mesenchymal stromal cells [1], are considered non-hematopoietic multipotent stem cells with self-renewal properties and the ability to differentiate into mesoderm tissues [2]. It has been hypothesized that the survival and proliferation of MSCs can be improved by maintaining cells at low O2 tension levels it remains unclear whether different in vitro concentrations of O2 over long periods of time change typical features of MSC [14]. Within this scenario, a relevant fact is that cultures under standard conditions (21% O2) are exposed to a significantly higher amount of O2 when compared with physiological in vivo conditions [17]. The present study discusses several described effects of hypoxia on MSC
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