The synergistic effect of surface topography and sustained release of TGF-β1 on myogenic differentiation of human mesenchymal stem cells

2016 ◽  
Vol 104 (7) ◽  
pp. 1610-1621 ◽  
Author(s):  
Samaneh Moghadasi Boroujeni ◽  
Shohreh Mashayekhan ◽  
Saeid Vakilian ◽  
Abdolreza Ardeshirylajimi ◽  
Masoud Soleimani
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synergistic Effect ◽  
Sustained Release ◽  
Surface Topography ◽  
Myogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Tgf Β1 ◽  
Effect Of Surface

Effect of Substrate Elasticity on In Vitro Aging of Human Mesenchymal Stem Cells

2012 ◽  
Vol 1498 ◽  
pp. 39-45
Author(s):  
Courtney E. LeBlon ◽  
Caitlin R. Fodor ◽  
Tony Zhang ◽  
Xiaohui Zhang ◽  
Sabrina S. Jedlicka
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Elastic Modulus ◽  
Myogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Immunofluorescent Staining ◽  
Differentiation Potential ◽  
Gene And Protein Expression ◽  
The Impact

ABSTRACTHuman mesenchymal stem cells (hMSCs) were routinely cultured on tissue-culture polystyrene (TCPS) to investigate the in vitro aging and cell stiffening. hMSCs were also cultured on thermoplastic polyurethane (TPU), which is a biocompatible polymer with an elastic modulus of approximately 12.9MPa, to investigate the impact of substrate elastic modulus on cell stiffening and differentiation potential. Cells were passaged over several generations on each material. At each passage, cells were subjected to osteogenic and myogenic differentiation. Local cell elastic modulus was measured at every passage using atomic force microscopy (AFM) indentation. Gene and protein expression was examined using qRT-PCR and immunofluorescent staining, respectively, for osteogenic and myogenic markers. Results show that the success of myogenic differentiation is highly reliant on the elastic modulus of the undifferentiated cells. The success of osteogenic differentiations is most likely somewhat dependent on the cell elastic modulus, as differentiations were more successful in earlier passages, when cells were softer.

scholarly journals Effect of RGOs on the Efficacy of Nkx2.5 Transfected Bone Marrow Mesenchymal Stem Cells Transplantation in Treatment Heart Failure in Rats

2020 ◽  
Author(s):  
Lin Wang ◽  
Bo Deng ◽  
Ran Zhang ◽  
Xingxing Hu ◽  
Yang Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Synergistic Effect ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Collagen I ◽  
Failure Models ◽  
Tgf Β1

Abstract Background: Heart failure (HF) is one of the major serious diseases to do harm to human health. Drugs, interventional treatment and heart transplantation are currently the main methods to treat HF. However, they fail to improve the patient's condition. Mesenchymal stem cells (MSCs) can regenerate functional cardiomyocytes and are promising to become a new therapeutic measure to treat heart failure. We assumed that Rehmannia glutinosa oligosaccharide (RGOs) has the synergistic effect with Nkx2.5 transfected MSCs (Nkx2.5) transplantation in treatment heart failure. Methods: MSCs and Nkx2.5 were preconditioned by RGOs. The apoptosis rate was detected by flow cytometry and the expressions of cardiac specific genes were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models were duplicated by injecting doxorubicin (total dose of 15mg/kg) intraperitoneally in male SD rats. When the models were prepared, rats were randomly divided into 6 groups: Control (CON), HF, MSCs, Nkx2.5, RGOs and RGOs combined with Nkx2.5 (RGOs+Nkx2.5) group. Echocardiography was used to detect cardiac function in rats. HE staining was used to observe the pathological changes of myocardium, and Masson staining was used to calculate the collagen volume fraction to detect the degree of myocardial fibrosis. The total mRNA was extracted to detect the following genes including cTnI, CX43, TGF-β1, Collagen I, MEF2 and GATA4 by Q-PCR. Protein of myocardial tissue was extracted to detect the expression of cTnI, CX43, MEF2 and GATA4, by western blot. Results: RGOs could not enhance cardiac specific gene expressions including CK, α-MHC, however it improved the survival of Nkx2.5 induced by H2O2 in vitro. In rat heart failure models, RGOs alone improved the heart pumping function and decreased collagen volume fraction (CVF), TGF-β1 and collagen I expression, and increased MEF2 and GATA4 mRNA expression. Moreover, RGOs cooperated with Nkx2.5 in improving left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Furthermore, RGOs and Nkx2.5 combination also increased CX43 expression, whereas decreased CVF and collagen I expression. Conclusion: RGOs has the synergistic effect with Nkx2.5 gene transfected MSCs transplantation in treatment with heart failure through decreasing myocardial fibrosis, inhibiting ventricular remodeling, and increasing the expressions of GATA4, MEF2.

Stro-1 Positive and Stro-1− Negtive Human Mesenchymal Stem Cells Express Different Levels of Immunosuppression.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4964-4964
Author(s):  
Dominique Thierry 9 ◽  
Y. Z. Zhang 1 ◽  
A. Chapel 2 ◽  
M. Benshidoum 3 ◽  
C. Mazurier 4 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lymphocyte Proliferation ◽  
Human Mesenchymal Stem Cells ◽  
Clinical Use ◽  
Soluble Factors ◽  
The Difference ◽  
Tgf Β1 ◽  
Selection Of

Abstract Mesenchymal stem cells (MSCs), have been shown to elicit immunosuppressive effect on allogeneic lymphocyte response. However, MSCs are heterogeneous and data on the inhibitory abilities of different MSC subsets are lacking. In the present study, we selected Stro-1+ cells from human bone marrow and evaluated the inhibitory capability of this MSC subset in mixed lymphocyte reactions (MLRs) or in mitogen stimulation asssays, in comparison to that of Stro-1− cells. To evaluate the two MSC subsets for immunomodulation in vitro, we added 1,000–30,000 Stro-1+ or Stro-1− cells to MLR at the beginning of the experiment. When comparing the inhibitory effects of the two subsets, PBLs proliferation was significantly more inhibited by Stro-1+MSCs (11.0%–63.7%) than by stro-1−MSCs (35.5%-106%) (P<0.01). Furthermore, as few as 1,000 Stro-1+ MSC could inhibit lymphocyte proliferation more effectively than 10 times more (10,000 cells) Stro-1−cells. As it was observed with the mixed lymphocyte reaction, suppression of the response to the mitogen also occurred in a dose dependent fashion, but to a lesser extent with the Stro-1−cells (25.5%–80.1% vs 7.5%–38.4% in Stro-1+cells) (P<0.05). To investigate whether the difference of suppressive effect that we observed between Stro-1+ and Stro-1− cells, still exist when MSC subsets are separated physically from PBL, we performed MLR in the upper chamber of a transwell and we seeded the lower chamber either with Stro-1+ or Stro-1− cells. The inhibitory effect of Stro-1+ cells was significantly more profound than the one observed when Stro-1− cells were used in the Transwell culture system (p<0.05) (Figure 3), demonstrating that one or several soluble factors was involved in production of different suppressive effects. Cytokine and chemokine genes, IL-10, TGF-β1, SDF-1, SCF and IL-6 expression were evaluated in both MSC subsets by quantitative RT-PCR. Low levels of IL-6, SCF, SDF-1 were observed in Stro-1+, which induced a fold increase around 1 (0,96 ± 0,32; 0,96 ± 0,24; 0,96 ± 0,24), indicating that there is no signifiant difference of these genes expression between the two MSC subsets. However, we observed in Stro-1+ a decreased gene expression for IL-10 (0,24 fold ± 0,59; p <0,05) and for TGF b1 (0,43 fold ± 0,32; p <0,05). This finding suggested that the candidate T-cell inhibitory factors TGF b1, IL-10, which are lower expressed in Stro-1+ cells, are not responsible for the more profound inhibition of immunoreactivity by Stro-1+ cells. We show here that significant differences do exist within these two subsets. Stro-1+ cells inhibit lymphocyte proliferation significantly more profoundly than Stro-1−cells. The difference is in part mediated by soluble factors, but not IL-10 and TGF-β1. These results point to the notion that Stro-1+ cells can elicit more powerful immunosuppressive ability and a pre-selection of Stro-1+MSC for clinical use may be advisable. These findings suggest that pre-selection of MSC before clinical use might produce more effective immunosuppression in different therapeutic applications, especially in clinics for the prevention of graft versus host disease (GVHD).

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