Preconditioning Approach in Stem Cell Therapy for the Treatment of Infarcted Heart

Haider, Khawaja Husnain; Ashraf, Muhammad

doi:10.1016/b978-0-12-398459-3.00015-0

Cited by 43 publications

(20 citation statements)

References 223 publications

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“…Thus, it may be possible to improve the survival of transplanted MSCs by further upregulating the expressions of angiogenic factors such as VEGF. To date, various approaches such as genetic modification and preconditioning have been utilized to improve posttransplantation survival of MSCs by reinforcing their paracrine effect [10,11,12,13]. In line with such efforts, we attempted to enhance angiogenesis by utilizing micro-RNAs (miRNA or miR) in the present study.…”

Section: Introductionmentioning

confidence: 82%

Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem Cells by Increasing Vascular Endothelial Growth Factor Secretion in the Ischemia/Reperfusion-Injured Heart

Seo

Lee

et al. 2017

J Vasc Res

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Adult stem cells have been studied as a promising therapeutic modality for the functional restoration of the damaged heart. In the present study, a strategy for enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a) influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSC^miR-146a) decreased the expression of neurofibromin 2, an inhibitor of p21-activated kinase-1 (PAK1). miR-146a also increased the expression of Ras-related C3 botulinum toxin substrate 1 and PAK1, which are known to induce VEGF expression, and the formation of vascular branches was increased in hMSC^miR-146a compared to hMSCs treated with VEGF. VEGF and p-Akt were increased in hMSC^miR-146a. Furthermore, injection of hMSC^miR-146a after ischemia/reperfusion (I/R) injury led to a reduction of fibrosis area and increased VEGF expression, confirming the regenerative capacity such as reparative angiogenesis in the infarcted area. Cardiac functions in I/R injury were improved following injection of hMSC^miR-146a compared to the I/R group. Taken together, these data suggest that miR-146 is a novel microRNA that regulates VEGF expression, and its use may be an effective strategy for enhancing the therapeutic efficacy of hMSC transplantation into the I/R-injured heart.

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Section: Introductionmentioning

confidence: 82%

Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem Cells by Increasing Vascular Endothelial Growth Factor Secretion in the Ischemia/Reperfusion-Injured Heart

Seo

Lee

et al. 2017

J Vasc Res

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“…Although most of the animals and clinical trials have confirmed stem cell transplantation is safe for the treatment of cardiac disease, but the therapeutic efficacy has been found insignificant [8,9,10,11,12,13,14]. Studies have shown that stem cells transplanted into damaged tissue die because of apoptosis and perhaps other forms of cell death as well, mostly in a week after transplantation [25,26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Existing evidence suggests that ischemia and hypoxia, inflammation, apoptosis, oxidative stress, and neuroendocrine activation together create a grim and adverse microenvironment in the infracted myocardium to threaten the survival of implanted stem cells [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Clearly, maximizing the survival rate of transplanted cells is a critical step towards maximizing the potential of stem cell therapy for AMI.…”

Section: Discussionmentioning

confidence: 99%

“…The recent advances in stem cell therapy from both basic and clinical researches have made regeneration of damaged vascular and cardiac tissues possible and demonstrated promising outcomes in the treatment of myocardial infarction [2,3,4,5,6]. However, in the setting of AMI, the harsh micro-environment in the infarct zone, which is filled with inflammatory response, oxidative stress, neuroendocrine activation, etc., imposes a negative impact on the survival of implanted cells and execution of their differentiation and biological functions [7,8,9,10,11,12,13,14]. Thus, the optimal efficacy of stem cell therapy in AMI has been largely hampered by the poor survival and low differentiated rates of the implanted stem cells into the myocardium.…”

Section: Introductionmentioning

confidence: 99%

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Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

Tian

et al. 2013

Cell Physiol Biochem

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Background/Aims: To investigate the beneficial effects of atorvastatin added to the cell therapy with bone marrow-derived mesenchymal stromal cells (BMSCs) in a rabbit model of acute myocardial infarction (AMI). Methods: Rabbits were randomly divided into control group (n=10), bone marrow stem cells transplantation group (n=10), and BMSCs + atorvastatin group (n=10). AMI was established by ligating the left descending coronary artery. The left ventricular (LV) function was evaluated by echocardiography. H&E staining and Masson's Trichrome staining were performed to evaluate inflammatory cell infiltration and cardiac fibrosis. Immunohistochemistry and TUNEL were conducted to assess survival, differentiation, and apoptosis of transplanted cells and cardiomyocytes. Results: BMSCs decreased LV systolic and diastolic diameters and increased LV ejection fractions, LV fractional shortening, LV systolic pressure and LV end-diastolic pressure. Atorvastatin synergistically enhanced the BMSCs-induced improvements of ischemic cardiac dysfunction. Atorvastatin reduced inflammatory cell infiltration, cardiac fibrosis, and derangement of myocardial morphology/structure. Atorvastatin added a protective effect to cardiomyocytes against apoptotic cell death in infarct and peri-infarct areas, and also increased the survival rate of implanted BMSCs in acute myocardial ischemia. Atorvastatin also promoted cardiac differentiation of implanted BMSCs in infarct myocardium. Conclusion: Atorvastatin acts to improve the microenvironment both by synergistically enhancing the existing effects of BMSCs and by adding new therapeutic effects to BMSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

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“…SCs affect tissue regeneration by modulating inflammation, which has revolutionized SC therapy for the treatment of inflammatory diseases [63]. For example, the transplantation of SCs for the treatment of myocardial infarction (MI) also suppresses inflammatory responses by significantly decreasing myocardial proinflammatory signaling molecules, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) [91].…”

Section: Enhanced Immune Regulationmentioning

confidence: 99%

The role of the microenvironment on the fate of adult stem cells

Dong

Hao

Han

et al. 2015

Sci. China Life Sci.

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Adult stem cells (SCs) exist in all tissues that promote tissue growth, regeneration, and healing throughout life. The SC niche in which they reside provides signals that direct them to proliferate, differentiate, or remain dormant; these factors include neighboring cells, the extracellular matrix, soluble molecules, and physical stimuli. In disease and aging states, stable or transitory changes in the microenvironment can directly cause SC activation or inhibition in tissue healing as well as functional regulation. Here, we discuss the microenvironmental regulation of the behavior of SC and focus on plasticity approaches by which various environmental factors can enhance the function of SCs and more effectively direct the fate of SCs.

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Preconditioning Approach in Stem Cell Therapy for the Treatment of Infarcted Heart

Cited by 43 publications

References 223 publications

Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem Cells by Increasing Vascular Endothelial Growth Factor Secretion in the Ischemia/Reperfusion-Injured Heart

Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem Cells by Increasing Vascular Endothelial Growth Factor Secretion in the Ischemia/Reperfusion-Injured Heart

Atorvastatin Improves Microenvironment to Enhance the Beneficial Effects of BMSCs Therapy in a Rabbit Model of Acute Myocardial Infarction

The role of the microenvironment on the fate of adult stem cells

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