A comparative analysis of human mesenchymal stem cell response to hypoxia in vitro: Implications to translational strategies

Abstract

Purpose: Mesenchymal stem cells (MSCs) are particularly valuable for structural tissue replacement. We compared the response to hypoxia among human MSCs derived from four different clinically relevant sources as an adjunct to translational developments.

Methods: Immunophenotypically indistinguishable human MSC lineages derived from bone marrow (bmMSCs), adipose tissue (adMSCs), amniotic fluid (afMSCs), and umbilical cord blood (cbMSCs) were submitted to either room air or 1% O2, under otherwise standard culture conditions. Cell expansion and quantitative RT-PCR data were obtained at different time points. Statistical analysis was by two-way mixed model and the F-test (P<0.05).

Results: The effect of hypoxia on expansion kinetics was dependent on cell source. Only prenatal sources of MSCs - afMSCs (P=0.002) and cbMSCs (P<0.001) - proliferated significantly faster under hypoxia than normoxia. Increased HIF1-alpha expression correlated consistently with increased cell expansion only among afMSCs. There were no significant variabilities in Survivin, Oct-4, and VEGF expressions.

Conclusions: Mesenchymal stem cell tolerance to hypoxia in vitro varies with cell source. Prenatal cells, particularly those derived from amniotic fluid, are more robust than their postnatal counterparts. HIF1-alpha may play a role in the amniotic fluid-derived cells' enhanced response. These findings should inform the choice of mesenchymal stem cells for prospective regenerative strategies.

Keywords: Adipose tissue mesenchymal stem cells; Amniotic mesenchymal stem cells; Bone marrow mesenchymal stem cells; Cord blood mesenchymal stem cells; Hypoxia; Mesenchymal stem cells; Regenerative medicine; Tissue engineering.