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.

A Systematic Review and Meta-analysis : Safety and Efficacy of Mesenchymal stem Cells Therapy for Heart Failure

2020 ◽  
Vol 15 ◽  
Author(s):  
Tiantian Shen ◽  
Lin Xia ◽  
Wenliang Dong ◽  
Jiaxue Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Safety And Efficacy ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF)，left ventricular end-systolic volume（LVESV），left ventricular end-diastolic volume（LVEDV） and brain natriuretic peptide（BNP） Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

2020 ◽  
Author(s):  
Guanyin Chen ◽  
wangqian zhang ◽  
Jintao Gu ◽  
Yuan Gao ◽  
Lei He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Patellar Tendon ◽  
Tendon Repair ◽  
Clinical Results ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Abstract Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

scholarly journals Mesenchymal Stem Cells Desensitize Castration-resistant Prostate Cancer to Docetaxel Chemotherapy via Inducing TGF-β1-mediated Cell Autophagy

2020 ◽  
Author(s):  
Yang Yu ◽  
Wen-tao Zhang ◽  
Fu-han Yang ◽  
Ya-dong Guo ◽  
Lin Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Tgf Β1

Abstract Background: Mesenchymal stem cells (MSCs) have been proved to accelerate prostate cancer (PCa) castration resistance progression. The purpose of this study is to investigate the contribution of MSCs to the development of docetaxel resistance in castration-resistant prostate cancer (CRPC) cells and its potential mechanisms.Methods: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in-vivo and in-vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses.Results: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel.Conclusions: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

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).

P0019MICROVESICLES FROM MESENCHYMAL STEM CELLS OVEREXPRESSING MIR-34A INHIBIT TGF-BETA-1-INDUCED EPITHELIAL-MESENVHYMAL TRANSITION IN RENAL TUBULAR EPITHELIAL CELLS IN VITRO

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Juan He ◽  
Yali Jiang ◽  
Yan Wang ◽  
Xiujuan Tian ◽  
Shiren Sun
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Notch Signaling ◽  
Notch Signaling Pathway ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Notch 1 ◽  
Renal Tubular ◽  
Tgf Β1

Abstract Background and Aims The application of microRNAs (miRNAs) in the therapy of kidney diseases is hampered by difficulties in delivering miRNAs effectively. Nano-sized microvesicles (MVs) are known as natural carriers of small RNAs. Our prior work has demonstrated that MVs isolated from mesenchymal stem cells (MSCs) attenuated kidney injuries induced by unilateral ureteral obstruction and 5/6 subtotal nephrectomy in mice. The present work aimed at evaluating the effects of miR-34a-5p (miR-34a)-modified MSC-MVs on transforming growth factor (TGF)-β1 induced fibrosis and apoptosis in vitro. Method Bone marrow MSCs were further modified by lentiviruses overexpressing miR-34a, and MVs were collected from these MSCs to treat HK-2 renal tubular cells exposed to TGF-β1. Alterations in epithelial-mesenchymal transition (EMT) and cell survival were further determined. Results We first demonstrated that MVs generated by miR-34a-modified MSCs contained more miR-34a. By analyzing the expression levels of epithelial markers (E-cadherin and Tight Junction Protein 1 (TJP1)) and mesenchymal markers (α-SMA and fibronectin), we found that the pro-fibrotic TGF-β1 induced EMT was remarkably suppressed by miR-34a-enriched MSC-MVs. Notch-1 receptor and Jagged-1 ligand, two major molecules of Notch signaling pathway, are predicted targets of miR-34a. We further found that the elevation in Notch-1 and Jagged-1 induced by TGF-β1 was inhibited by miR-34a-enriched MSC-MVs. The inhibitory effects of miR-34a-enriched MSC-MVs on EMT and Notch signaling pathway were stronger than the control MSC-MVs. In addition, TGF-β1 exposure also induced apoptosis in HK-2 cells. Although miR-34amofidied MSC-MVs could inhibit TGF-β1-triggered apoptosis in HK-2 cells, the effects were less significant than the control MSC-MVs. This phenomenon may be resulted from the pro-apoptotic effects of miR-34a. Conclusion Our study demonstrates that miR-34a-overexpressing MSC-MVs inhibit EMT induced by pro-fibrotic TGF-β1 in renal tubular epithelial cells, possibly through inhibiting Jagged-1/Notch-1 pathway. Genetic modification of MSC-MVs with anti-fibrotic molecule may present a novel strategy for treatment of renal injuries.

Enhanced bioactivity of transform growth factor-β1 from sulfated chitosan microspheres for in vitro chondrogenesis of mesenchymal stem cells

2014 ◽  
Vol 86 (12) ◽  
pp. 1885-1895 ◽  
Author(s):  
Feifei Li ◽  
Lie Ma ◽  
Bo Li ◽  
Changyou Gao
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
In Vitro Release ◽  
Transform Growth Factor ◽  
Blank Group ◽  
Chitosan Microspheres ◽  
Tgf Β1

Abstract Transform growth factor-β1 (TGF-β1) is an extremely powerful protein to induce the chondrogenesis of mesenchymal stem cells (MSCs) both in vitro and in vivo. However, due to the short-life of TGF-β1, the direct application of TGF-β1 may deteriorate its bioactivity and thereby the repair effect. In this study, uniform sulfated chitosan microspheres (SCMs) with a mean diameter of ∼ 2 μm were fabricated by membrane emulsification as a carrier for TGF-β1. The in vitro release study showed that TGF-β1 could be sustainedly released from the microspheres up to 16 days. Under the protection of SCMs, about 13 % TGF-β1 was preserved even after stored for 14 days. The microspheres cytotoxicity was evaluated by coculture of MSCs with different concentrations SCMs and no obvious deterioration of cell viability was observed when the concentration of SCMs is lower than 2 μg/1.0 × 104 cells. In comparison with the blank group, the addition of TGF-β1 either in free state or loaded in SCMs inhibited the proliferation trend of MSCs. Quantitative analysis of GAGs production and genes expression of COL II and aggrecan by qRT-PCR revealed that enhanced bioactivity of TGF-β1 was obtained in the group of TGF-β1/SCMs, indicating that SCMs could be functioned as a promising carrier of TGF-β1 for the in vitro chondrogenesis of MSCs.

scholarly journals The Outcome of Bisphosphonate-Related Osteonecrosis of the Jaw Patients’ Gingiva-Derived Mesenchymal Stem Cells on Wound Healing in a Mice Excisional Skin Model.

2021 ◽  
Author(s):  
Mengyu Li ◽  
Yejia Yu ◽  
Jiajia Wang ◽  
Yuqiong Zhou ◽  
Yueqi Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Cell Survival ◽  
Osteonecrosis Of The Jaw ◽  
Skin Model ◽  
Group A ◽  
Tgf Β1

Abstract Background: Retarded gingival healing is the hallmark of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and poses a great challenge to maxillofacial surgeons. Although previous studies have showed that bisphosphonates (BPs) are highly toxic to healthy gingival mesenchymal stem cells (GMSCs) in vitro, there is overall lack of direct evidence demonstrating the regeneration capacity of oral mucosa in BRONJ patients. In present study, we aim to isolate GMSCs from BRONJ patients’ gingiva and assessed their phenotypes and functions in vitro, as well as their therapeutic effects for wound healing in a mice excisional skin model. Methods: BRONJ patients’ gingival samples were used for microarray analysis, histological detection and cell culture. The stem cells isolated from the central gingiva (center-BRONJ GMSCs) and the peripheral lesions (peri-BRONJ GMSCs) were analyzed by Cell Counting Kit-8 (CCK-8), cell adhesion, scratch and flow cytometry. Luciferase/GFP (Green Fluorescent Proteins)-labeled GMSCs combined with Hydrogel were transplanted in a mice excisional skin model, and mice were divided into a hydrogel alone group, a hydrogel/control GMSCs group, a hydrogel/center-BRONJ GMSCs group and a hydrogel/peri-BRONJ GMSCs group. Bioluminescence imaging trace cell survival in vivo. Healing effects were evaluated by wound area measurement, histology, immunohistochemistry (IH) and immunofluorescence (IF). Results: Center-BRONJ GMSCs and peri-BRONJ GMSCs were all fibroblast-like cells, but they became slender and more wrinkled compared control GMSCs. Notably, they exhibited decreased proliferation, adhesion, migration capacities and underwent early apoptosis in vitro. In animal model, BRONJ GMSCs transplantation also displayed lower cell survival rate and poor healing effects than that of control group. Mechanistically, we found that the expression of TGF-β1 signaling pathway was suppressed not only in BRONJ patients’ gingival lesions but also in BRONJ GMSCs transplantation animal model. Conclusions: In BRONJ patients’ microenvironment, the regeneration ability of oral mucosa was dramatically decreased. Our mice skin model demonstrated for the first time that BRONJ GMSCs transplantation displayed poor effects on wound healing mainly via suppressing TGF-β1 signaling pathway. This study provides new insights into the prevention for BRONJ by improving the functions of GMSCs in accelerating gingival wound healing.

scholarly journals Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing TGF-β1-mediated cell autophagy

2020 ◽  
Author(s):  
Yang Yu ◽  
Wen-tao Zhang ◽  
Fu-han Yang ◽  
Ya-dong Guo ◽  
Lin Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Tgf Β1

Abstract Background: Mesenchymal stem cells (MSCs) have been proved to accelerate prostate cancer (PCa) castration resistance progression. The purpose of this study is to investigate the contribution of MSCs to the development of docetaxel resistance in castration-resistant prostate cancer (CRPC) cells and its potential mechanisms. Methods: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in-vivo and in-vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses. Results: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel. Conclusions: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

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