Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleYalnız künye2025Scopus SJRQ2Therapeutic potential of adult stem cells-derived mitochondria transfer combined with curcumin administration into ARPE-19 cells in age-related macular degeneration model
Kılıç, Kamil Can; Duruksu, Gökhan; Öztürk, Ahmet; Rençber, Selenay Furat; Kılıç, Buket; Yazır, Yusufhan
Objective: Mitochondria transfer from human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs-mt) and human endometrium-derived mesenchymal stem cells (hE-MSCs-mt), along with curcumin, were explored as potential treatments for age-related macular degeneration (AMD) caused by mitochondrial inefficiency, using a retinal model to assess impacts of curcumin and hWJ-MSCs-mt or hE-MSCs-mt on AMD. Methods: ARPE-19 cells established an in vitro AMD model. Cells were exposed to 0–50 μM curcumin for 24 hours to determine optimal concentration by assessing their viability. Immunofluorescence examined SOD1, TNF-α, and TGF-β levels at optimal hydrogen peroxide (H2O2) concentration. β-galactosidase staining and DCFH analysis evaluated H2O2-induced cellular senescence. Immunofluorescence assessed REP65, CRALBP1 (RLBP1), Pink1, and Parkin expression, whereas qRT-PCR analyzed Nrf2, Ire1a, ARMS2, HTRA1, RPE65, RLBP1, NOX4, and TOMM20 expression following co-treatment with curcumin and hWJ-MSCs-mt or hE-MSCs-mt. Results: Curcumin improved ARPE-19 cell survival under H2O2-induced oxidative stress by regulating SOD1, TNF-α, TGF-β, DCFH, and MDA levels. hWJ-MSCs-mt transfer increased RLBP1 and Parkin expression, whereas curcumin reduced Parkin expression. hE-MSCs-mt transfer upregulated Parkin, RPE65, Pink1, and RLBP1 expressions, with curcumin enhancing RPE65 expression. hWJ-MSCs-mt and curcumin combined more effectively downregulated expressions of stress-related genes (Nrf2, Ire1α, NOX4) and improved expression of mitochondrial function gene (TOMM20). hE-MSCs-mt transfer with curcumin synergistically enhanced expression of retinal health markers (RPE65, RLBP1) and downregulated expression of damage-associated genes (HTRA1, ARMS2) in AMD models. Conclusion: Curcumin combined with hWJ-MSCs-mt or hE-MSCs-mt is a potential AMD therapy owing to its anti-inflammatory properties; however, further in vivo and human studies are needed to confirm its efficacy and safety.
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İncele - MakaleYalnız künye2024Scopus SJRQ2Investigation of the differentiation potential of pericyte cells as an alternative source of mesenchymal stem cells
Polat, Selen; Yazir, Yusufhan; Duruksu, Gökhan; Kiliç, Kamil Can; Mert, Serap; Gacar, Gülçin; Öncel Duman, Büşra; Halbutoğullari, Zehra Seda
Background: The mesenchymal stem cells (MSCs) with characterized by their multipotency and capacity to differentiate into various tissue cell types, have led to their incorporation in regenerative medicine research. However, the limited numbers of MSCs in the human body and their diverse differentiation capabilities in tissues highlight the need for exploring alternative regenerative cell sources. In this study, therefore, we conducted molecular level examinations to determine whether pericytes, specialized cell communities situated near blood vessels, could serve as a substitute for human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this context, the potential application of pericytes surrounds the vessels when MSCs are insufficient for functional purposes. Methods: The pericytes utilized in this investigation were derived from the placenta and characterized at the third passage. Similarly, the hBM-MSCs were also characterized at the third passage. The pluripotent properties of the two cell types were assessed at the gene expression level. Thereafter, both pericytes and hBM-MSCs were directed towards adipogenic, osteogenic and chondrogenic differentiation. The cells in both groups were examined on days 7, 14, and, 21 and their differentiation status was compared both immunohistochemically and through gene expression analysis. Results: Upon comparing the pluripotency characteristics of placental pericytes and hBM-MSCs, it was discovered that there was a substantial upregulation of the pluripotency genes FoxD3, Sox2, ZPF42, UTF1, and, Lin28 in both cell types. However, no significant expression of the genes Msx1, Nr6a1, Pdx1, and, GATA6 was observed in either cell type. It was also noted that pericytes differentiate into adipogenic, osteogenic and, chondrogenic lineages similar to hBM-MSCs. Discussion: As a result, it has been determined that pericytes exhibit high differentiation and proliferation properties similar to those of MSCs, and therefore can be considered a suitable alternative cell source for regenerative medicine and tissue engineering research, in cases where MSCs are not available or insufficient. It is notable that pericytes have been suggested as a potential substitute in studies where MSCs are lacking.
AtıfScopus11WoS11OpenAlex11İncele - MakaleAçık Erişim2024Scopus SJRQ2Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering
Duman, Büşra Öncel; Yazir, Yusufhan; Halbutoğullari, Zehra Seda; Mert, Serap; Öztürk, Ahmet; Gacar, Gülçin; Duruksu, Gökhan
Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluated in vitro and in vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl-1 on the 10th day dropped to 168 mg dl-1 on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.
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