scholarly journals Enhancement of Functionality and Therapeutic Efficacy of Cell-Based Therapy Using Mesenchymal Stem Cells for Cardiovascular Disease

2019 ◽  
Vol 20 (4) ◽  
pp. 982 ◽  
Author(s):  
Chul Yun ◽  
Sang Lee
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Efficacy ◽  
Clinical Findings ◽  
Current Status ◽  
Paracrine Effects ◽  
Cell Based Therapy ◽  
Effective Therapeutic Strategy ◽  
Ischemic Diseases

Cardiovascular disease usually triggers coronary heart disease, stroke, and ischemic diseases, thus promoting the development of functional failure. Mesenchymal stem cells (MSCs) are cells that can be isolated from various human tissues, with multipotent and immunomodulatory characteristics to help damaged tissue repair and avoidance of immune responses. Much research has proved the feasibility, safety, and efficiency of MSC-based therapy for cardiovascular disease. Despite the fact that the precise mechanism of MSCs remains unclear, their therapeutic capability to treat ischemic diseases has been tested in phase I/II clinical trials. MSCs have the potential to become an effective therapeutic strategy for the treatment of ischemic and non-ischemic cardiovascular disorders. The molecular mechanism underlying the efficacy of MSCs in promoting engraftment and accelerating the functional recovery of injury sites is still unclear. It is hypothesized that the mechanisms of paracrine effects for the cardiac repair, optimization of the niche for cell survival, and cardiac remodeling by inflammatory control are involved in the interaction between MSCs and the damaged myocardial environment. This review focuses on recent experimental and clinical findings related to cardiovascular disease. We focus on MSCs, highlighting their roles in cardiovascular disease repair, differentiation, and MSC niche, and discuss their therapeutic efficacy and the current status of MSC-based cardiovascular disease therapies.

scholarly journals Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

2016 ◽  
Vol 96 (3) ◽  
pp. 1127-1168 ◽  
Author(s):  
Samuel Golpanian ◽  
Ariel Wolf ◽  
Konstantinos E. Hatzistergos ◽  
Joshua M. Hare
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Coronary Vessels ◽  
Heart Tissue ◽  
Structure And Function ◽  
Nonischemic Cardiomyopathy ◽  
Cell Based Therapy ◽  
And Function

Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.

scholarly journals Potential and Therapeutic Efficacy of Cell-based Therapy Using Mesenchymal Stem Cells for Acute/chronic Kidney Disease

2019 ◽  
Vol 20 (7) ◽  
pp. 1619 ◽  
Author(s):  
Chul Yun ◽  
Sang Lee
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Therapeutic Efficacy ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Diverse Range ◽  
Cell Based Therapy

Kidney disease can be either acute kidney injury (AKI) or chronic kidney disease (CKD) and it can lead to the development of functional organ failure. Mesenchymal stem cells (MSCs) are derived from a diverse range of human tissues. They are multipotent and have immunomodulatory effects to assist in the recovery from tissue injury and the inhibition of inflammation. Numerous studies have investigated the feasibility, safety, and efficacy of MSC-based therapies for kidney disease. Although the exact mechanism of MSC-based therapy remains uncertain, their therapeutic value in the treatment of a diverse range of kidney diseases has been studied in clinical trials. The use of MSCs is a promising therapeutic strategy for both acute and chronic kidney disease. The mechanism underlying the effects of MSCs on survival rate after transplantation and functional repair of damaged tissue is still ambiguous. The paracrine effects of MSCs on renal recovery, optimization of the microenvironment for cell survival, and control of inflammatory responses are thought to be related to their interaction with the damaged kidney environment. This review discusses recent experimental and clinical findings related to kidney disease, with a focus on the role of MSCs in kidney disease recovery, differentiation, and microenvironment. The therapeutic efficacy and current applications of MSC-based kidney disease therapies are also discussed.

Directions for Enhancement of the Therapeutic Efficacy of Mesenchymal Stem Cells in Different Neurodegenerative and Cardiovascular Diseases: Current Status and Future Perspectives

2021 ◽  
Vol 16 ◽  
Author(s):  
Lamiaa A. Ahmed ◽  
Khaled F. Al-Massri
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Current Status ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Apoptotic Effects

: Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in a wide variety of medical conditions including neurodegenerative disorders and cardiovascular diseases. Although preliminary research has emphasized the ability of MSCs to engraft at sites of injury, several studies have revealed that MSCs mediate their effects through release of various paracrine factors, and through their antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. However, the clinical implications of MSCs application are limited due to their low survival rate in conditions of inflammation, oxidative stress, and nutrient restriction in damaged areas. Furthermore, the function of isolated MSCs is usually affected by the patient’s health. Therefore, it is necessary to develop new methods to enhance the therapeutic efficacy of MSCs under pathophysiological conditions. This review provides an overview of the general properties of MSCs, their therapeutic potential in neurodegenerative disorders such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease, as well as cardiovascular diseases such as myocardial infarction, diabetic cardiomyopathy, and dilated cardiomyopathy, and their related mechanisms. In addition, this review also discusses potential problems and side effects, as well as current and future directions for improvement of MSCs therapy and their implications and applications.

scholarly journals Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Shujing Li ◽  
Xianyun Wang ◽  
Jing Li ◽  
Jun Zhang ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebrovascular Disease ◽  
Diabetic Foot ◽  
Therapeutic Potential ◽  
Current Status ◽  
Ischemic Disease ◽  
Ischemic Cerebrovascular Disease ◽  
Ischemic Diseases

Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs’ survival and residential ratein vivo, timing of transplantation, particular microenvironment, and patient’s clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases.

scholarly journals FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

2020 ◽  
Author(s):  
Jingyu Deng ◽  
Ning Zhang ◽  
Yong Wang ◽  
Chao Yang ◽  
Chao Xin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Efficacy ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Hypoxic Stress ◽  
Paracrine Effects

Abstract Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5-OV in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that FNDC5-MSCs treatment improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

scholarly journals FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

2020 ◽  
Author(s):  
Jingyu Deng ◽  
Ning Zhang ◽  
Yong Wang ◽  
Chao Yang ◽  
Yabin Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Efficacy ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Hypoxic Stress ◽  
Paracrine Effects

Abstract Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

scholarly journals FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

2020 ◽  
Author(s):  
Jingyu Deng ◽  
Ning Zhang ◽  
Yong Wang ◽  
Chao Yang ◽  
Chao Xin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Efficacy ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Hypoxic Stress ◽  
Paracrine Effects

Abstract Background The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc + –eGFP + ) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5 +/+ in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5 +/+ . Results Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5 +/+ alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that MSCs FNDC5+/+ treatment improved the survival of transplanted MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo . Furthermore, MSCs FNDC5+/+ therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

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