Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

Zhao, Lingyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

doi:10.1016/j.yexcr.2016.03.024

Cited by 87 publications

(72 citation statements)

References 37 publications

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“…MSCs have been reported to provide tendon-bone healing with an ideal bio-environment and accelerate tendon reintegration into bone to re-establish biomechanical properties. Other studies have shown that the high potential of MSCs to promote tendon-bone healing may result from: (1) the spontaneous migration of MSCs to an injured site due to the local inflammation environment [57]; (2) the biological and mechanical environment of the tendon-bone junction, which enhances proliferation and differentiation of MSCs into multiple lineages to repair damaged tissues [58, 59]; and (3) the “trophic” effects of MSCs by the secretion of different cytokines and molecules that promote angiogenesis, modulation of the inflammatory response, prevention of scar formation and recruitment of tendon intrinsic progenitor cells to the interface [60]. The results of this study demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of MSCs and TCs in tendon-bone healing.…”

Section: Discussionmentioning

confidence: 99%

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Song

Jiang

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL) reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs) and tendon cells (TCs). Methods: The effect of continuous passive motion (CPM) therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

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Section: Discussionmentioning

confidence: 99%

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Song

Jiang

Wang

et al. 2017

Cell Physiol Biochem

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“…Likewise, IGF-1 overexpression in ASCs improved the EF 6 weeks after cell transplantation into rats suffering from MI [488]. Zhao and colleagues induced overexpression of HGF in MSCs following administration into a mouse model of MI [489]. In addition to increased survival of modified MSCs probably induced by increased B cell lymphoma (Bcl)-2 and reduced Bax and caspase-3 levels [490], the authors detected an enhancement of angiogenesis, LVEF and proliferation capacity of resident cardiomyocytes upon SC treatment [489].…”

Section: Genetic Sc Modificationsmentioning

confidence: 99%

“…Zhao and colleagues induced overexpression of HGF in MSCs following administration into a mouse model of MI [489]. In addition to increased survival of modified MSCs probably induced by increased B cell lymphoma (Bcl)-2 and reduced Bax and caspase-3 levels [490], the authors detected an enhancement of angiogenesis, LVEF and proliferation capacity of resident cardiomyocytes upon SC treatment [489]. Moreover, overexpression of anti-apoptotic factors like Bcl-xL and Bcl-2 was found to positively influence the viability and therapeutic efficiency of applied SCs [491,492].…”

Section: Genetic Sc Modificationsmentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

161

140

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A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

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“…Salvianolic acid B (Sal B) was reported to attenuate the apoptosis of MSC [40] , and transplantation of Sal B pretreated MSCs in rats improves cardiac function partly through the paracrine mechanism and promotes the differentiation of MSC toward endothelium cells [41] . Hepatocyte growth factor (HGF), an important cytokine for angiogenesis, antiinflammation and anti-apoptosis, was associated with enhanced angiogenesis, less cardiomyocyte apoptosis, increased proliferation of cardiomyocytes, and cardio-protective effects in a mouse MI model [42] . However, currently the differentiation rate of transplanted bone marrow stem cells is relatively low, the fate of transplanted cells and whether MSCs will affect the function of other normal cells in vivo is not clear.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

New Strategies for Myocardial Infarction Treatment

Peng

Zhou

2017

Journal of Cardiology and Therapy

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At present, the treatments of myocardial infarction mainly focus on the recanalization of the occluded coronary artery to restore perfusion and prevent myocardial necrosis. To do this, commonly used methods include drug therapy, thrombolytic therapy, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery. Drug therapiesTraditional drug therapies include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone receptor antagonists, β-receptor blockers, and so on [1][2][3] . The main purpose of these treatments is the prevention of left ventricular remodeling. Thrombolytic therapy ABSTRACTMyocardial infarction is due to lasting and serious myocardial ischemia that leads to myocardial necrosis and cardiac remodeling, and can consequently result in heart failure. Traditional treatment for myocardial infarction includes drug therapy, thrombolytic therapy, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery. Although these treatments can to some extent relieve the symptom of myocardial ischemia, they fail to repair the necrotic heart tissues. Myocardial regeneration is undoubtedly the best solution to the clinical problems of myocardial infarction treatment. The review briefly illustrated the pros and cons of the traditional treatments of myocardial infarction, and focused on the application of new strategies for myocardial infarction treatment using myocardial regeneration.

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Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

Cited by 87 publications

References 37 publications

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

New Strategies for Myocardial Infarction Treatment

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