Browsing by Subject "Mesenchymal Stem Cells"

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Open Access
Effect of estrogen on apoptotic regulatory mechanisms in mesenchymal stem cell maintenance
(2006) Terzioğlu, Ece
Mesenchymal Stem Cells (MSCs) can both self-renew and differentiate into fat, bone, cartilage, and muscle. They have a high therapeutic value due to their differentiation potential and nonimmunogenic characteristics, however their rareness and duration of their culture are the main handicaps in their application in cell-based therapies. Therefore, our aim was to explore the possible mechanisms that are involved in MSC maintenance and proliferation by using rat MSCs as a model. We studied the effect of estrogen on MSCs due to its role in growth regulation, differentiation, and cellular proliferation. In MSCs isolated from both normal and ovariectomized animals, the number and the CFU activity were increased when cultured with estrogen. To reveal the mechanism of the action of estrogen on MSC maintenance, we investigated the apoptotic pathway since estrogen has been shown to have a detrimental effect on apoptosis in other systems. The number of apoptotic cells decreased when MSCs were cultured in the presence of estrogen. To elucidate the molecular mechanism of estrogen’s effect on MSC apoptosis, we examined the expression of the bcl-2 family of genes. The expression of anti- apoptotic Bcl-2 and Bcl-xL proteins increased in the presence of estrogen, whereas the expression of proapoptotic Bak decreased. Our results clearly show that estrogen increases the number of the functional MSCs by differentially regulating the expression of the bcl-2 family of genes and inhibiting apoptosis. Therefore estrogen treatment of MSCs may offer a potential to increase the number of MSC for treatments.
Open Access
Role of environmental factors in mesenchymal stem cell biology
(2009) Gültekin, Sinan
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).
Open Access
Small functional groups presented on peptide nanofibers for determining fate of rat mesenchymal stem cells
(2014) Yaşa, Öncay
Glycosaminoglycans (GAGs) are negatively-charged, unbranched polysaccharides that play important roles in various biological processes and are vital for the regeneration of damaged tissues. Like other natural extracellular matrix components, glycosaminoglycans and proteoglycans show considerable variation in local concentration and chemical composition depending on tissue type. They are found in various connective tissues, including bone, cartilage and fat, and display strong water-binding capacity due to their negative charges. Mechanical characters of GAGs are heavily influenced by the degree and pattern of sulfation, which may greatly alter their viscoelasticity and physiological functions. Variations in GAG sulfation patterns are created principally through extracellular matrix modeling. Due to their extracellular matrix-organizing abilities, glycosaminoglycans are promising biomacromolecules for the design of new bioactive materials for tissue engineering and tissue reconstruction applications. In this study, we functionalized peptide amphiphile molecules with carboxylate and sulfonate groups to develop nanofibrous networks displaying a range of chemical patterns, and evaluated the effect of the chemical groups over the differentiation fate of rat mesenchymal stem cells. We demonstrate that higher sulfonate-to-glucose ratios are associated with adipogenesis, while higher carboxylate-to-glucose ratios resulted in chondrogenic and osteogenic differentiation of the rat mesenchymal stem cells.