Journal of Stem Cell Research & Therapy

Hypoxia in stem cell niche: How stromal cells answer on low oxygen demand?

7^th Annual Conference on Stem Cell and Regenerative Medicine

August 04-05, 2016 Manchester, UK

Buravkova L B, Lobanova M V, Andreeva E R, Sotnezova E V and Buravkov S V

Russian Academy of Sciences, Russia

Posters & Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Multipotent mesenchymal stem cells (MSCs) play an important role in the regulation of stem cell niche, where low oxygen tension seems to be a common in vivo feature. Recently we have demonstrated that MSCs permanently expanded at low; the niche comparable (1-5%) O2 displayed an increased proliferation, attenuation of osteo and adipo differentiation, delay of replicative senescence, which is based on changes in energetic metabolism. The data of the global gene expression array demonstrated the up-regulation of genes responsible for cell signaling, proliferation, motility/migration and cellular metabolism and down-regulation of cytoskeleton, electron transfer and extracellular matrix proteins�?? genes. It is generally considered that the most of the hypoxic effects are regulated HIFs proteins, primarily by HIF-1a. By RT-PCR analysis we detected the different dynamics in expression of HIF family proteins. After permanent expansion at 5% O2 the HIF-1a and HIF-3α expression was the same as at 20% O2, while at 1% O2 HIF-1a was down-regulated and on the contrary, HIF-3α was up-regulated. Under hypoxia the expression of apoptosis-associated genes (BAX, DAPK3 & CASP1) was reduced, proliferation-associated genes were upregulated (IGF2, IL1A, MT3, VEGFа & GPI). After MSC/HSPCs (hematopoietic stem and progenitor cells) interaction, the up-regulation of cell adhesion molecule genes (ICAM-1, VCAM-1, CDH1), and down-regulation of genes involved in matrix remodeling (COLs, MMPs, TIMPs, ADAMs, HAS1) and cell-matrix contacts (ITGs) was demonstrated with RT- PCR. These data indicate on activation of MSCs, which most effectively increased at 5% O2. Indeed, the number of CFCs at 5 % O2 was 1.6 times higher than at 20% �?2 due to increase in number of multipotent precursors BFU-E, CFU-GEMM and CFU-GM. These changes were at least partly ensured by increased concentration of MCP-1 and IL-8at 5% O2.Our data demonstrate that MSCs in hypoxic micro-environment significantly modulate their physiology and ensure a better maintenance/expansion of HSPCs, pointing to the hypoxia as a physiological regulatory factor as well as a cell engineering tool.

Biography :

Email: buravkova@imbp.ru