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-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 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.

scholarly journals Hematopoietic stem cells can differentiate into pericytes and myofibroblast in wound healing, not bone Mesenchymal stem cells

2020 ◽  
Author(s):  
Yanan Kong ◽  
Liuhanghang Cheng ◽  
Min Xuan ◽  
Hao Ding ◽  
Biao Cheng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Bone Mesenchymal Stem Cells ◽  
Hematopoietic Stem ◽  
Green Fluorescent

Abstract Background Hematopoietic stem cells(HSCs) and mesenchymal stem cells(MSCs) can participate in wound healing. However, very few studies had shown HSCs and MSCs could arrive to the wound and differentiate into tissues. In this study, we intend to investigate the role of bone marrow HSCs and MSCs in wound healing. Methods We first removed the bone marrow of mice by irradiation. Furthermore, we injected different colours of fluorescent HSCs and MSCs into the tail vein of irradiated mice to reconstruct bone marrow function. We prepared wound models on the back of these mice. In vivo imaging and immunohistochemical staining were used to track the expression of fluorescent protein. Results HSCs and MSCs have been isolated and cultured. HSCs expressed expressed Sca1, not lineage, CD34 or CD48. MSCs expressed expressed CD29 and CD44,not CD34 or CD45. HSCs labeled with green fluorescent protein reached the wound and co-expressed with desmin and α-SMA. MSCs didn’t stay on the wound. Conclusions The results show HSCs in the bone marrow of mice can directly participate in wound healing and differentiate into pericytes and myofibroblasts.

Non-Hematopoietic Bone Marrow Cells Can Be Mobilized and Differentiate into Cardiomyocytes after Myocardial Infarction: Possible Contribution of Mesenchymal Stem Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2694-2694
Author(s):  
Hiroshi Kawada ◽  
Jun Fujita ◽  
Kentaro Kinjo ◽  
Yumi Matsuzaki ◽  
Mitsuyo Tsuma ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Fluorescent Protein ◽  
Bone Marrow Cells ◽  
Side Population ◽  
Myocardial Tissue ◽  
Hematopoietic Stem ◽  
Cardiac Tissues

Abstract Recent studies have suggested that bone marrow (BM) cells can contribute to regeneration processes in various tissues. Cardiomyocytes derived from BM cells have been observed after myocardial infarction (MI), and BM-derived cells mobilized by cytokines were capable of regenerating the myocardial tissue, leading to an improvement in survival or cardiac function after MI. However, the responsible BM cells have not been fully identified. The most likely candidates for the BM-derived stem cells with the ability to regenerate myocardial tissue are hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC). The aim of this study was to determine the precise origin of the BM cells mobilized by cytokines to repair infarcted myocardium. Here, we used two independent clonal studies; we transplanted genetically marked single HSC or clonal MSC into lethally-irradiated recipient mice, induced MI, treated the mice with G-CSF, and analyzed the cardiac tissues. First, we transplanted single CD34−c-kit+Sca-1+lineage− side population (CD34−KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally-irradiated mice, induced myocardial infarction (MI), and treated the animals with G-CSF to mobilize stem cells to the damaged myocardium. At 8 weeks post-MI, from 100 specimens we counted only 3 EGFP+actinin+ cells in myocardium of CD34−KSL-SP cells-transplanted mice, but more than 5,000 EGFP+actinin+ cells in whole BM cell-transplanted mice, suggesting that most of EGFP+actinin+ cells derived from non-hematopoietic BM cells. These results suggested that the major population of cells mobilized from the BM and active in the regeneration of cardiomyocytes was non-hematopoietic in origin. Next, clonally purified mesenchymal stem cells, CMG cells, transfected with a pMLC2v-EGFP plasmid encoding EGFP driven by the myosin light chain promoter were transplanted directly into BM of lethally-irradiated mice, MI was induced, and they were treated with G-CSF. As a result, a number of EGFP+actinin+ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggested that the vast majority of BM-derived cardiomyocytes are of mesenchymal origin.

Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3581-3587 ◽  
Author(s):  
Hiroshi Kawada ◽  
Jun Fujita ◽  
Kentaro Kinjo ◽  
Yumi Matsuzaki ◽  
Mitsuyo Tsuma ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Enhanced Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Side Population ◽  
Specific Manner ◽  
Green Fluorescent ◽  
Stimulating Factor

Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)–derived cardiomyocytes. First, we transplanted single CD34– c-kit+Sca-1+ lineage– side population (CD34–KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP+ actinin+ cells in myocardium of CD34– KSL-SP cells in mice that received transplants, but more than 5000 EGFP+ actinin+ cells in whole BM cell in mice that received transplants, suggesting that most of EGFP+ actinin+ cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP+ actinin+ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.

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