İnsan mezenkimal kök hücrelerinin moleküler seviyede karakterizasyonu ve tanımlanması.


Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Türkiye

Tezin Onay Tarihi: 2012

Tezin Dili: İngilizce

Öğrenci: Ceren Aksoy

Danışman: FERİDE SEVERCAN

Özet:

Bone marrow mesenchymal stem cells (BM-MSCs) are pluripotent cells that can differentiate into a variety of non-hematopoietic tissues. They also maintain healthy heamatopoiesis by providing supportive cellular microenvironment into BM. In this thesis, MSCs were characterized in terms of their morphological, immunophenotypical and differentiation properties. Then, they were examined by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy together with hierarchical clustering, and FTIR microspectroscopy. In the first part of this study, global structural and compositional changes in BM-MSCs during beta thallasemia major (-TM) were investigated. The significant increase in lipid, protein, glycogen and nucleic acid concentrations in thalassemic MSCs with respect to healthy MSCs were attributed to enhanced cell proliferation and BM activity during ineffective erytropoiesis (IE). MTT assay results reflected increase in cellular activity of thallasemic BM-MSCs. The significant decreases in the concentrations of the mentioned macromolecules after BM transplantation therapy were interpreted as recovery of IE. Based on these changes, sampling groups were successfully discriminated by using cluster analysis. In the second part of this study, it was aimed to identify new molecular marker(s) in order to determine the effects of donor age on healthy BM-MSCs. The spectral results reflected that there were significant increases in the concentrations of saturated lipids, proteins, glycogen and nucleic acids in children and adolescent group BM-MSCs when compared with the infants, early and mid adults. These results were interpreted as increased proliferation activity in younger BM-MSCs. The results of MTT assay clarified the increased cellular activity. Spectral data of five different sampling groups was discriminated by hierarchical cluster analysis. The FTIR microspectroscopic imaging study was also performed in two different parts of the study in order to support the ATR-FTIR spectroscopy results. The FTIR microspectroscopic results were found in agreement with ATR-FTIR spectroscopy results.