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.

scholarly journals Adipose-derived mesenchymal stem cells (ADMSCs) protect against hyperglycemia and hyperlipidemia-induced heart failure by inhibiting autophagy-related apoptosis

2021 ◽  
Author(s):  
Xu Xu ◽  
Lingyun Tao ◽  
Jie zhou ◽  
Jing Ni
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Metabolic Disorder ◽  
Body Weight Loss ◽  
Heart Tissue ◽  
Myocardial Cells ◽  
Glucose Levels

Abstract Background Mesenchymal stem cells (MSCs), a type of seed cell, are expected to improve impaired diabetic cardiac function. Inflammation and autophagy play an important role in the development of metabolic disorder-induced heart failure. The aim of this work was to assess the effect of adipose-derived mesenchymal stem cells (ADMSCs) on metabolic disorder-induced heart failure and the underlying mechanisms. Methods Eight weeks old male C57BL/6 mice were randomly divided into three groups: normal chow mice (NC group), high-fat diet-fed and streptozotocin-treated mice (HFD+STZ group) and mice administered with ADMSCs-once per week for 3 months after the mice were treated with HFD+STZ (ADMSCs+HFD+STZ group). Once a week lipid and glucose levels were measured and echocardiography was performed. Immunohistochemistry was used to detect the adhesion of macrophages in heart tissue in all three groups. 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 by 33mM glucose in the presence or absence of IL-1β. Transmission electron microscopy, mRFG-GFP-LC3 assays 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 the administration of ADMSCs. The administration of ADMSCs also remits 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 cells stimulated with high glucose, which eventually led to apoptosis and cardiac dysfunction. Conclusions This study confirmed that ADMSCs may have potential for use in improving cardiac function by restraining autophagy and apoptosis of myocardial cells. We also identified the roles of the IL-1β in hyperglycemia- and hyperlipidemia-induced cardiac injuries, which may be a key factor for diabetic complications.

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo

Gut ◽  
2008 ◽  
Vol 58 (4) ◽  
pp. 570-581 ◽  
Author(s):  
H Aurich ◽  
M Sgodda ◽  
P Kaltwasser ◽  
M Vetter ◽  
A Weise ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Hepatocyte Differentiation ◽  
Adipose Tissue In Vitro

Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo

2016 ◽  
Vol 473 (4) ◽  
pp. 1111-1118 ◽  
Author(s):  
Nhu Thuy Trinh ◽  
Toshiharu Yamashita ◽  
Tran Cam Tu ◽  
Toshiki Kato ◽  
Kinuko Ohneda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Improve Wound Healing

scholarly journals Hypoxia Inducible Factor-1α Overexpression Enhances the Efficacy of Mesenchymal Stem Cells Derived Extracellular Vesicles for Cardiac Repair After Myocardial Infarction

2021 ◽  
Author(s):  
Qingjie Wang ◽  
Le Zhang ◽  
Zhiqin Sun ◽  
Boyu Chi ◽  
Ailin Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Extracellular Vesicles ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Sprague Dawley

Abstract Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1a engineered mesenchymal stem cells (MSCs) in a rat model of AMI.Methods and Results EVs isolated from HIF-1a engineered MSCs (HIF-1a-EVs) and control MSCs (MSCs-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with MSCs-EVs, HIF-1a-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1a-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1a-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1a-EVs. After miR-221-3p was inhibited in HIF-1a-EVs, the biological effects of HIF-1a EVs on apoptosis and angiogenesis were attenuated.Conclusion EVs released by MSCs with HIF-1a overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1a engineered MSC-derived EVs.

scholarly journals Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway

2020 ◽  
Author(s):  
Ying Liu ◽  
Dan Lin ◽  
Haiyang Zhang ◽  
Huiya Wang ◽  
Ting Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Luciferase Reporter ◽  
Differentiation Capacity ◽  
Healthy Donors ◽  
Adipose Mesenchymal Stem Cells ◽  
Polymerase Chain

Abstract BACKGROUNDCancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODSOil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTSWe showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSIONGC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.

scholarly journals Adipose tissue-derived mesenchymal stem cells differentiated into hepatocyte-like cells in vivo and in vitro

2014 ◽  
Vol 11 (3) ◽  
pp. 1722-1732 ◽  
Author(s):  
LIBO YIN ◽  
YUHUA ZHU ◽  
JIANGANG YANG ◽  
YIJIANG NI ◽  
ZHAO ZHOU ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue

scholarly journals Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Peter Succar ◽  
Edmond J. Breen ◽  
Donald Kuah ◽  
Benjamin R. Herbert
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Disease Progression ◽  
Proinflammatory Cytokines ◽  
Mechanism Of Action ◽  
Stromal Vascular Fraction ◽  
Slow Disease Progression

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc)in vitroand measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1αdecreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation usingin vivomodels.

Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo

2008 ◽  
Vol 32 (S1) ◽  
pp. 51-55 ◽  
Author(s):  
M. Del Bue ◽  
S. Riccò ◽  
R. Ramoni ◽  
V. Conti ◽  
G. Gnudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Platelet Concentrates
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