scholarly journals Human umbilical cord mesenchymal stem cells derived Exosomes attenuate injury of myocardial infarction by miR-24-3p-promoted M2 macrophage polarization

2021 ◽  
Author(s):  
Feng Zhu ◽  
Yihuan Chen ◽  
Jingjing Li ◽  
Ziying Yang ◽  
Yang Lin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Pathway Activation ◽  
M2 Macrophage Polarization

Abstract Background- Exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs-Exo) were recommended as ideal substitutes for cell-free cardiac regenerative medicine, which had presented encouraging effects in regulating inflammation and attenuating myocardial injury. The phenotype of macrophages resident in myocardium were regulated dynamically in response to environmental cues, which may either protect against injury or promote maladaptive remodeling. However, the underlying mechanisms about UMSCs-Exo regulating macrophage polarization are still not well understood. Herein, we aimed to explore the effects of UMSCs-Exo on macrophage polarization and their roles in cardiac repair after myocardial infarction (MI). Methods and Results- Exosomes were isolated from the supernatant of human umbilical cord mesenchymal stem cells (UMSCs) and transplanted by intramyocardial injection after MI. Our results showed that UMSCs-Exo improved cardiac function by increasing M2 macrophage polarization and reducing excessive inflammation. After depletion of macrophages with clodronate liposomes, the therapeutic effects of UMSCs-Exo were disrupted. Administrated with UMSC-Exo, macrophages are inclined to polarize towards M2 phenotype in inflammatory environment in vitro. The results of RNA-sequencing indicated Plcb3 was a key gene concerned in UMSCs-Exo facilitated M2 macrophage polarization. Further bioinformatics analysis revealed exosomal miR-24-3p as a potential effector mediated Plcb3 down regulation in macrophages. Increasing miR-24-3p expression in macrophages effectively enhanced M2 macrophage polarization by suppressing Plcb3 expression and NF-κB pathway activation in inflammatory environment. Furthermore, diminishing miR-24-3p expression in UMSCs-Exo attenuated the effects of UMSCs-Exo on M2 macrophage polarization. Conclusions- Our study demonstrated that macrophages, as important inflammatory regulators, participated in UMSCs-Exo mediated myocardial repair after MI. And the therapeutical effects were at least partially carried out by UMSCs-Exo promoting M2 macrophage polarization in an inflammatory microenvironment. Mechanically, exosomal miR-24-3p inhibits the expression of Plcb3 and NF-κB pathway activation to promote M2 macrophage polarization.

scholarly journals The Therapeutic Effects of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells on Scleroderma

2021 ◽  
Author(s):  
Yue Yu ◽  
Liangliang Shen ◽  
Xiaoyun Xie ◽  
Jingjun Zhao ◽  
Miao Jiang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
M1 Macrophage

Abstract Background: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. Methods: Mice with scleroderma received a single 50 μg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. Results: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. Conclusion: We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycin-induced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

scholarly journals Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Jing Ni ◽  
Xijun Liu ◽  
Yiheng Yin ◽  
Peiyu Zhang ◽  
Ya-Wei Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Umbilical Cord ◽  
Rat Model ◽  
Therapeutic Option ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Ecm Remodeling

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.

scholarly journals MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against renal injury in diabetic nephropathy through facilitating M2 macrophage polarization by targeting TRAF6

2021 ◽  
Author(s):  
Yaqi Zhang ◽  
Xi Le ◽  
Shuo Zheng ◽  
Ke Zhang ◽  
Jing He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
High Throughput ◽  
Renal Injury ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Human Umbilical Cord ◽  
M2 Macrophage Polarization

Abstract Background Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease, but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation. Methods This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell line and UC-MSCs-derived conditional medium was used to assess the involvement of macrophage polarization signaling. Results UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an antiinflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting TRAF6-STAT1 signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement. Conclusions Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. It will pave the way for the use of UC-MSCs for therapeutic delivery of miRNAs targeted at kidney diseases.

scholarly journals Therapeutic Effects of CUR-Activated Human Umbilical Cord Mesenchymal Stem Cells on 1-Methyl-4-phenylpyridine-Induced Parkinson’s Disease Cell Model

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Li Jinfeng ◽  
Wang Yunliang ◽  
Liu Xinshan ◽  
Wang Yutong ◽  
Wang Shanshan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pc12 Cells ◽  
Umbilical Cord ◽  
Cell Model ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Proliferation And Differentiation

The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) activated by curcumin (CUR) on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+), a cell model of Parkinson’s disease (PD). The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR) were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH) and microtubule associated protein-2 (MAP2) and significantly decreased the expression of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.

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