scholarly journals Role of Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Cardiac Tissue and Improvement of Cardiac Function: a Narrative Review

2020 ◽  
Vol 11 (1) ◽  
pp. 8446-8456
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Trichostatin A ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Point Of View

Recent efforts have made in order to novel therapeutic approaches to reduce the heavy cardiovascular burden. The use of cell therapy and applying stem cell-based therapies has received much attention; of particular interest are adipose-derived mesenchymal stem cells (ADSCs). The present review aimed to review the studies which examined and researched various aspects of ADSCs to improve cardiac function. A comprehensive review of all articles assessed and discussed the application of ADSCs in the improvement of cardiac tissue renewing and cardiomyocytes regeneration was planned and conducted by the two reviewers. The initial literature search revealed a total of 153 articles that, of those, 34 were considered eligible. From the perspective of heart tissue regeneration, the inductive role of ADSCs in sensing mechanical stimulation and produce collagen and elastin scaffolds, vascularizing cardiac tissue, and exosomes (vesicles derived from ADSCs) in ADSCs‐mediated myocardial protection has indicated. In the process of ADSCs differentiation to cardiomyocyte- like cells, the role of various targeted pathways have been identified that can be influenced by different elements such as TGF-beta1, phorbol myristate acetate, Angiotensin II, Rho-associated kinases, 5-Azaytidine, Sodium valproate, fibrin scaffold and trichostatin A have been highlighted. In the final, from a therapeutic point of view, the effectiveness of ADMSCs differentiation to cardiomyocytes as improving left ventricular functional state has been discussed. Summarizing the studies confirms a significant improvement in cardiac function following direct application of ADSCs or their transformation to cardiomyocytes by stimulating or inhibiting various cellular pathways leading reducing oxidative stress and inflammatory bed, reducing cardiomyocyte apoptosis, attenuating cardiac fibrosis, reducing the infiltration of immune cells and collagen deposition, and enhancing angiogenesis.

P6292Role of CXCL12gamma isoform and its interactions with heparan-sulfates in post-ischemic cardiac remodeling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Duval ◽  
I Zlatanova ◽  
Y Sun ◽  
P Alayrac ◽  
I Gomez ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Cardiac Tissue ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Vascular Growth ◽  
Heparan Sulfates

Abstract Introduction Myocardial infarction (MI) is a severe ischemic disease precipitating long-term adverse remodeling and heart failure. The chemokine CXCL12/SDF-1 is essential for cardiovascular system development and plays a prominent role in physio-pathological processes such as inflammation, angiogenesis and tissue fibrosis. In addition to the binding to its cognate receptors CXCR4 and CXCR7, CXCL12 interacts with heparan-sulfates (HS) which coordinate its biological activity. We have previously highlighted the essential role of CXCL12/HS interactions in vascular growth and remodeling in the setting of critical limb ischemia. In addition, studies in experimental model of MI revealed a protective role for the CXCL12α isoform, through the regulation of cardiomyocyte survival and recruitment of inflammatory cells. However, in mice, three CXCL12 isoforms (α, β and γ) have been identified and, among them, the CXCL12γ isoform shows an unchallenged ability to cooperate with HS, suggesting a putative pivotal role in tissue repair. Objectives The aim of the study is to analyze the role of CXCL12γ isoform and the importance of CXCL12/HS interactions in post-ischemic cardiac remodeling in an acute model of MI. Methods MI was induced by permanent ligation of the left ascending coronary artery in mice carrying a Cxcl12 gene mutation that precludes interactions with HS (Cxcl12Gagtm) and in Cxcl12γ knock-in animals (Cxcl12γ-KI) harboring CXCL12γ deficiency. Alternatively, the impact of CXCL12γ overexpression and the importance of its interactions with HS was also evaluated in wild-type (WT) mice receiving transcutaneous echo-guided injections of adenovirus encoding WT Cxcl12γ or HS-binding-disabled Cxcl12γ in cardiac tissue. Cardiac function and remodeling have been assessed through echocardiography analysis, evaluation of infarct size, interstitial fibrosis, vascular growth (capillary and arteriole densities) and inflammatory cell infiltration into the cardiac tissue. Results After MI, Cxcl12Gagtm and Cxcl12γ-KI animals exhibit reduction in cardiac function and adverse left ventricular remodeling when compared to their respective WT littermates. Interestingly, overexpression of CXCL12γ in WT mice cardiac restored cardiac function by reducing the size of the infarcted area, interstitial fibrosis and promoting vascular growth. In sharp contrast, HS–binding disabled CXCL12gamma mutants failed to improve cardiac function and to abrogate adverse left ventricular remodeling. Conclusion We show that CXCL12γ isoform plays an important role in the regulation of post-ischemic cardiac function and remodeling and that its interactions with HS are essential for adequate cardiac repair in the setting of acute MI.

scholarly journals Mesenchymal stem cells from human amniotic membrane differentiate into cardiomyocytes and endothelial-like cells without improving cardiac function after surgical administration in rat model of chronic heart failure

2019 ◽  
Vol 11 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Fazel Gorjipour ◽  
Ladan Hosseini-Gohari ◽  
Alireza Alizadeh Ghavidel ◽  
Seyed Javad Hajimiresmaiel ◽  
Nasim Naderi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Troponin T ◽  
Left Ventricular ◽  
Border Zone ◽  
Vascular Endothelial ◽  
Tissue Fibrosis

Introduction: Human amnion-derived mesenchymal stem cells (hAMSCs) have been used in the treatment of acute myocardial infarction. In the current study, we investigated the efficacy of hAMSCs for the treatment of chronic model of myocardial ischemia and heart failure (HF) in rats. Methods: Male Wistar rats weighing between 250 to 350 g were randomized into three groups: sham, HF control and HF+hAMSCs. For HF induction, animals were anesthetized and underwent left anterior descending artery ligation. In HF+hAMSCs group, 2×106 cells were injected into the left ventricular muscle four weeks post ischemia in the border zone of the ischemic area. Cardiac function was studied using echocardiography. Masson’s trichrome staining was used for studying tissue fibrosis. Cells were transduced with green fluorescent protein (GFP) coding lentiviral vector. Immunohistochemistry was used for detecting GFP, vascular-endothelial growth factor (VEGF) and troponin T markers in the tissue sections. Results: Assessment of the cardiac function revealed no improvement in the myocardial function compared to the control HF group. Moreover, tissue fibrosis was similar in two groups. Immunohistochemical study revealed the homing of the injected hAMSCs to the myocardium. Cells were stained positive for VEGF and troponin T markers. Conclusion: injection of hAMSCs 4 weeks after ischemia does not improve cardiac function and cardiac muscle fibrosis, although the cells show markers of differentiation into vascular endothelial cells and cardiomyocytes. In sum, it appears that hAMSCs are effective in the early phases of myocardial ischemia and does not offer a significant advantage in patients with chronic HF.

scholarly journals Intramyocardial Injected Human Umbilical Cord-Derived Mesenchymal Stem Cells (Hucmscs ) Contribute to the Recovery of Cardiac Function and the Migration of CD4+ T Cells into the Infarcted Heart via CCL5/CCR5 Signaling

2021 ◽  
Author(s):  
Jing Liu ◽  
Xiaoting Liang ◽  
Mimi Li ◽  
Fang Lin ◽  
Xiaoxue Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Cardiac Function ◽  
Umbilical Cord ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Human Umbilical Cord ◽  
Intramyocardial Injection

Abstract Background: Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods: HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function, angiogenesis, fibrosis and hypertrophy, and immune cells infiltration were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. Results: HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells in the heart with HucMSC than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in the HucMSCs treated heart compared to the control. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or C-C Motif Chemokine receptor 5 (CCR5) antagonist significantly reversed this effect. Conclusion: These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ regulatory T cells and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.

Bone marrow mesenchymal stem cells overexpressing GATA-4 improve cardiac function following myocardial infarction

Perfusion ◽  
2019 ◽  
Vol 34 (8) ◽  
pp. 696-704 ◽  
Author(s):  
Ji-Gang He ◽  
Hong-Rong Li ◽  
Bei-Bei Li ◽  
Qiao-Li Xie ◽  
Dan Yan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cardiac Function ◽  
Cardiac Tissue ◽  
Cell Group ◽  
Marrow Mesenchymal Stem Cells

Introduction: The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone. Methods: A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit. Results: In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells. Conclusion: GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI.

scholarly journals MiR-34a inhibitor protects mesenchymal stem cells from hyperglycaemic injury through the activation of the SIRT1/FoxO3a autophagy pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fengyun Zhang ◽  
Fei Gao ◽  
Kun Wang ◽  
Xiaohong Liu ◽  
Zhuoqi Zhang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Cardiac Function ◽  
Cell Viability ◽  
High Glucose ◽  
Autophagy Pathway ◽  
Precise Role

Abstract Background Mesenchymal stem cells (MSCs) are favourable treatments for ischaemic diseases; however, MSCs from diabetic patients are not useful for this purpose. Recent studies have shown that the expression of miR-34a is significantly increased in patients with hyperglycaemia; the precise role of miR-34a in MSCs in diabetes needs to be clarified. Objective The aim of this study is to determine the precise role of miR-34a in MSCs exposed to hyperglycaemia and in recovery heart function after myocardial infarction (MI) in diabetes mellitus (DM) rats. Methods DM rat models were established by high-fat diet combined with streptozotocin (STZ) injection. MSCs were isolated from the bone marrow of donor rats. Chronic culture of MSCs under high glucose was used to mimic the DM micro-environment. The role of miR-34a in regulating cell viability, senescence and paracrine effects were investigated using a cell counting kit-8 (CCK-8) assay, senescence-associated β-galactosidase (SA-β-gal) staining and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) ELISA, respectively. The expression of autophagy- and senescence-associated proteins in MSCs and silent information regulator 1 (SIRT1) and forkhead box class O 3a (FoxO3a) were analysed by western blotting. Autophagic bodies were analysed by transmission electron microscopy (TEM). The MI model was established by left anterior descending coronary artery (LAD) ligation, and then, the rats were transplanted with differentially treated MSCs intramuscularly at sites around the border zone of the infarcted heart. Thereafter, cardiac function in rats in each group was detected via cardiac ultrasonography at 1 week and 3 weeks after surgery. The infarct size was determined through a 2,3,5-triphenyltetrazolium chloride (TTC) staining assay, while myocardial fibrosis was assessed by Masson staining. Results The results of the current study showed that miR-34a was significantly increased under chronic hyperglycaemia exposure. Overexpression of miR-34a was significantly associated with impaired cell viability, exacerbated senescence and disrupted cell paracrine capacity. Moreover, we found that the mechanism underlying miR-34a-mediated deterioration of MSCs exposed to high glucose involved the activation of the SIRT1/FoxO3a autophagy pathway. Further analysis showed that miR-34a inhibitor-treated MSC transplantation could improve cardiac function and decrease the scar area in DM rats. Conclusions Our study demonstrates for the first time that miR-34a mediates the deterioration of MSCs’ functions under hyperglycaemia. The underlying mechanism may involve the SIRT1/FoxO3a autophagy signalling pathway. Thus, inhibition of miR-34a might have important therapeutic implications in MSC-based therapies for myocardial infarction in DM patients.

Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis

2004 ◽  
Vol 287 (6) ◽  
pp. H2670-H2676 ◽  
Author(s):  
Noritoshi Nagaya ◽  
Takafumi Fujii ◽  
Takashi Iwase ◽  
Hajime Ohgushi ◽  
Takefumi Itoh ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Intravenous Administration ◽  
Diastolic Pressure ◽  
Troponin T ◽  
Left Ventricular ◽  
Control Group

Mesenchymal stem cells (MSCs) are pluripotent cells that differentiate into a variety of cells, including cardiomyocytes and endothelial cells. However, little information is available regarding the therapeutic potency of systemically delivered MSCs for myocardial infarction. Accordingly, we investigated whether intravenously transplanted MSCs induce angiogenesis and myogenesis and improve cardiac function in rats with acute myocardial infarction. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. At 3 h after coronary ligation, 5 × 106 MSCs (MSC group, n = 12) or vehicle (control group, n = 12) was intravenously administered to Lewis rats. Transplanted MSCs were preferentially attracted to the infarcted, but not the noninfarcted, myocardium. The engrafted MSCs were positive for cardiac markers: desmin, cardiac troponin T, and connexin43. On the other hand, some of the transplanted MSCs were positive for von Willebrand factor and formed vascular structures. Capillary density was markedly increased after MSC transplantation. Cardiac infarct size was significantly smaller in the MSC than in the control group (24 ± 2 vs. 33 ± 2%, P < 0.05). MSC transplantation decreased left ventricular end-diastolic pressure and increased left ventricular maximum dP/d t (both P < 0.05 vs. control). These results suggest that intravenous administration of MSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium.

Adipose Tissue Derived Mesenchymal Stem Cells (ADMSCs) Protect Against Hyperglycemia and Hyperlipidemia Induced Heart Failure by Inhibiting Autophagy Related Apoptosis

2021 ◽  
Author(s):  
Xu Xu ◽  
Sujing Qiang ◽  
Lingyun Tao ◽  
Jie Zhou ◽  
Jing Ni
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cardiac Function ◽  
Metabolic Disorder ◽  
Myocardial Cell ◽  
Heart Tissue

Abstract Background Mesenchymal stem cells (MSCs), kinds of seed cells, are expected to improve impaired diabetic cardiac function. Inflammation and autophagy play the important role in the development of metabolic disorder induced heart failure. The aim of this work was to assess the effect of adipose tissue derived mesenchymal stem cells (ADMSCs) on metabolic disorder induced heart failure and the underlying mechanisms. Methods In vivo, 8 weeks old male C57BL/6 mice were randomly divided into three groups: normal chaw mice (sham group), high fat diet fed and streptozotocin intraperitoneal injected mice (HFD + STZ group) and ADMSCs tail intravenous injected per week for 3 months after the mice were treated with HFD + STZ (ADMSCs + HFD + STZ group). The lipid and glucose levels as well as echocardiography were measured per week. Immunohistochemistry was used to detect the adhesion of macrophages in heart tissue among three groups. Besides, inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-8(CXCL-15) were measured by western blot or RT-qPCR. In vitro, H9c2 cardiomyocytes were stimulated to 33mM glucose in the presence or absence of IL-1β. Transmission electron microscope, mRFG-GFP-LC3 assay and flow cytometry were used to investigate autophagy related apoptosis in H9c2 cells. Results HFD + STZ treated mice presented significant cardiac hypertrophy, body weight loss, hyperglycemia and hyperlipidemia. However, these changes were remarkably reversed by ADMSCs administration. The administration of ADMSCs also remit histological alterations and deposition of collagen in the heart tissue. Furthermore, ADMSCs downregulated the adhesion of macrophages in heart tissue. More importantly, IL-1β from macrophages increased the autophagy of myocardial cell stimulated with high glucose which eventually leaded to their apoptosis and the following cardiac dysfunction. Conclusions This study confirmed that ADMSCs may have potential for use in improving cardiac function by restraining autophagy and apoptosis of myocardial cell. We also found the roles of the IL-1β in hyperglycemia and hyperlipidemia induced cardiac injuries, which may be a key factor for diabetic complications.

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