Role of environmental factors in mesenchymal stem cell biology

Abstract

Mesenchymal Stem Cells (MSCs) have the abilities of self-renewal and differentiation into fat, bone, cartilage, and muscle tissues. Besides intrinsic mechanisms that control the fate of the MSCs, extrinsic physiological factors also play role in this decision. Therefore, our aim is to explore the effects of possible environmental factors, involved in MSC maintenance by using rat MSCs as a model. We studied the effects of hypoxia and estrogen on growth regulation and cellular proliferation in MSCs. MSCs cells exhibited high colony number in hypoxic conditions and the expansion of MSCs was increased addition of the estrogen. In addition, estrogen prevents apoptosis, under hypoxic condition. The effects of estrogen on the expression levels of Notch genes (Notch1, Notch2, Notch3 and Notch4) were also investigated. In order to understand the possible mechanism of estrogen response, an experimental and in silico approach are used. The expression levels of Notch1 and Notch 3 were decreased treatment and the expression level of Notch 4 was increased upon estrogen treatment. In addition, bioinformatics analysis showed that, estrogen upregulates ERG family transcription factors, ELF family transcription factors, HOXL4 family transcription factors, KLF family transcription factors and transcription factor SOX3, which bind to Notch 1 transcriptional regulatory region, implying indirect effects of estrogen on Notch 1 expression. Twenty biomaterials were also investigated in order to assess whether they provide an appropriate environment for MSCs expansion. It was found that eight of the biomaterials out of twenty designated as, CA-1, CA-2, CA-3, CI-K, CI-A, CIII-1, CIII-2 and CIII-3, were appropriate candidates to expand MSCs. The combination polymers designated as HPMA/PEG provided appropriate conditions when prepared in the proportion of 1:0 (CA-1), 1:1 (CA-2) and 2:1 (CA-3). The appropriate proportion of polymers designated as HEMA/PEG/HPC was 2:1:1(CIII-1), 3:0:1 (CIII-2) and 1:1:0 (CIII-5).