scholarly journals Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells

2014 ◽  
Vol 5 (4) ◽  
pp. 103 ◽  
Author(s):  
Janina Frisch ◽  
Jagadeesh Venkatesan ◽  
Ana Rey-Rico ◽  
Gertrud Schmitt ◽  
Henning Madry ◽  
...  
2021 ◽  
Vol 41 ◽  
pp. 603-615
Author(s):  
A-N Zeller ◽  
◽  
M Selle ◽  
Z Gong ◽  
M Winkelmann ◽  
...  

Underlying pathomechanisms of osteoporosis are still not fully elucidated. Cell-based therapy approaches pose new possibilities to treat osteoporosis and its complications. The aim of this study was to quantify differences in human bone marrow-derived mesenchymal stem cells (hBMSCs) between healthy donors and those suffering from clinically manifest osteoporosis. Cell samples of seven donors for each group were selected retrospectively from the hBMSC cell bank of the Trauma Department of Hannover Medical School. Cells were evaluated for their adipogenic, osteogenic and chondrogenic differentiation potential, for their proliferation potential and expression of surface antigens. Furthermore, a RT2 Osteoporosis Profiler PCR array, as well as quantitative real-time PCR were carried out to evaluate changes in gene expression. Cultivated hBMSCs from osteoporotic donors showed significantly lower cell surface expression of CD274 (4.98 % ± 2.38 %) than those from the control group (26.03 % ± 13.39 %; p = 0.007), as assessed by flow cytometry. In osteoporotic patients, genes involved in inhibition of the anabolic WNT signalling pathway and those associated with stimulation of bone resorption were significantly upregulated. Apart from these changes, no significant differences were found for the other cell surface antigens, adipogenic, osteogenic and chondrogenic differentiation ability as well as proliferation potential. These findings supported the theory of an influence of CD274 on the regulation of bone metabolism. CD274 might be a promising target for further investigations of the pathogenesis of osteoporosis and of cell-based therapies involving MSCs.


2008 ◽  
Vol 15 (9) ◽  
pp. 553-562 ◽  
Author(s):  
I A W Ho ◽  
K Y W Chan ◽  
L Miao ◽  
W S N Shim ◽  
C M Guo ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3848-3848
Author(s):  
Marilena Ciciarello ◽  
Valentina Salvestrini ◽  
Davide Ferrari ◽  
Sara Gulinelli ◽  
Roberta Zini ◽  
...  

Abstract Abstract 3848 Introduction: Human bone marrow derived Mesenchymal Stem Cells (hMSCs) are adult multipotent cells. hMSCs differentiate in vitro and in vivo into several tissue lineages originating from the three germinal layers making them attractive candidates for bioengineering and cellular therapy. Thus, it seems of great relevance to search putative messengers and signalling able to modulate their proliferation and differentiation. Nucleotides triphosphates are extracellular messengers binding to specific receptors (P2Rs) that modulate cell functions depending on the cell type. Controversial information is available on P2 expression and activity in hMSCs. Methods and Results: Here we found that hMSCs expressed several P2R subtypes. hMSCs were very resistant to the cytotoxic effects of high concentrations of ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that ATP treatment down-regulated cell proliferation and up-regulated cell migration genes in hMSCs. Functional studies confirmed the inhibitory activity of ATP on proliferation and clonogenic ability of hMSCs. Furthermore, ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, xenotransplant experiments showed that the homing capacity of hMSCs to murine bone marrow was increased by ATP pre-treatment. Moreover, ATP increased pro-inflammatory cytokines production (IL-2, IFN-g, IL-12p70), while decreased secretion of the anti-inflammatory cytokine IL-10. This finding was associated with the reduced ability of ATP-treated hMSC of inhibiting T-cell proliferation. Microarrays data suggested that several genes implicated in hMSC differentiation can be modulated by ATP treatment. To further investigate this issue, hMSCs cells were cultured under adipogenic or osteogenic conditions and were transiently exposed to ATP before starting differentiation or continuously exposed to ATP for the first 3 days of differentiation induction. We demonstrated that adipogenesis-related accumulation of lipids, analyzed by Oil red O staining, was more evident in ATP treated cultures. Furthermore, quantitative real time PCR (qRT-PCR) assay showed that mRNA expression of PPARg, a transcription factor early up-regulated during adipogenesis, was significantly increased in hMSCs differentiated cells treated with ATP. In osteogenic condition, analysis of mineralized area through Alizarin Red staining, indicated that ATP treatment enhanced the extent of mineralization compared to untreated control. The expression of RUNX2, a key transcription factor in osteogenesis, analyzed by qRT-PCR in differentiated cells confirmed data obtained in Alizarin-based assay. Conclusions: These data demonstrated that purinergic signalling modulates biological functions and differentiation potential of hMSCs. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 8 (A) ◽  
pp. 508-511
Author(s):  
Gusti Revilla ◽  
Henny Mulyani

BACKGROUND: Research on human bone marrow mesenchymal stem cells (hBM-MSCs) for burns healing has been known to increase the percentage of integrin expression of α2β1, type I collagen, transforming growth factor-β, and matrix metalloproteinases-9, but research on giving hBM-MSCs to growth factor expression in the process of re-epithelialization of burn healing has not been done. AIM: This study aims to the effect of hBM-MSCs given on the expression of epidermal growth factor (EGF) and EGF receptor (EGFR) in the process re-epithelialization in the healing of burn experimental rat. MATERIALS AND METHODS: This research is experimental with the post-test only control design, using 30 Wistar rats. Rats were divided into two groups, namely, control (phosphate-buffered saline), and the treatment was given hBM-MSCs, and stem cells were given subcutaneous doses of 2 × 106 cells/ml. Before being treated rats were anesthetized using xylazine and ketamine then the rats were burned in the dorsal (spine) with full-thickness. On the 3, 7, and 14 days, skin tissue was taken to see the expression of EGF and EGFR by immunohistochemical methods. This study was approved by the Ethics Commission of the Faculty of Medicine, Andalas University, Padang. The results of the study were analyzed by the t-test. RESULTS: Immunohistochemical examination of EGF and EGFR expressions after hBM-MSCs administration has significantly increased epithelialization compared with controls. Increased EGF expression was found on days 3 and 7 with moderate positive internal revenue service (IRS) assessment and on day 14 strong positive EGF expression, as well as EGFR expression on days 3 and 7 with moderate positive IRS assessment and on day 14 robust positive EGFR expression. CONCLUSION: This study concluded that giving of hBM-MSCs can increase the expression of EGF and EGFR which enhances the process of re-epithelialization thereby accelerating the healing of burns of experimental rats.


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