| dc.description.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). | en_US |
