Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction
Abstract Background Multipotent mesenchymal stromal cell (MSC) therapy has been widely recognized as a feasible strategy for regenerating injured myocardial tissue. However, little is known about the efficacy of intravenous injection of allogeneic umbilical cord (UC) MSCs in preclinical models of po...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-018-0888-z |
| _version_ | 1818203653937299456 |
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| author | Meikuang Lim Weiqiang Wang Lu Liang Zhi-bo Han Zongjin Li Jie Geng Meng Zhao Honghong Jia Jie Feng Zhe Wei Baoquan Song Jiemin Zhang Jun Li Tianwen Liu Fan Wang Ting Li Jianming Li Yihu Fang Jianhua Gao Zhongchao Han |
| author_facet | Meikuang Lim Weiqiang Wang Lu Liang Zhi-bo Han Zongjin Li Jie Geng Meng Zhao Honghong Jia Jie Feng Zhe Wei Baoquan Song Jiemin Zhang Jun Li Tianwen Liu Fan Wang Ting Li Jianming Li Yihu Fang Jianhua Gao Zhongchao Han |
| author_sort | Meikuang Lim |
| collection | DOAJ |
| description | Abstract Background Multipotent mesenchymal stromal cell (MSC) therapy has been widely recognized as a feasible strategy for regenerating injured myocardial tissue. However, little is known about the efficacy of intravenous injection of allogeneic umbilical cord (UC) MSCs in preclinical models of porcine myocardial infarction. Methods Different dosages of allogeneic UC-MSCs or the vehicle [phosphate-buffered saline (PBS)] were delivered intravenously into an acute myocardial infarction (AMI) porcine model twice after coronary ligation. Echocardiography was performed to examine the cardiac function and single photon emission computed tomography (SPECT) and positron emission tomography (PET)/computed tomography (CT) was performed to detect cardiac perfusion and nonviable myocardium. At the end of the experiment, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Masson T staining were performed to determine the infarct area. The protein and gene expression levels associated with cardiac function, inflammation, and angiogenesis were examined by Western blot and real time polymerase chain reaction (PCR). In vivo trafficking of intravenous injection of allogeneic UC-MSCs enhanced green fluorescent protein (eGFP) was detected by real time PCR and immunofluorescence. Results After systemic delivery, allogeneic UC-MSCs were largely distributed in the lungs and some in the infracted myocardium. At week 8 following AMI, echocardiography demonstrated significantly improved fractional shortening in the high-dose (1.5 × 106 cells/kg) group. SPECT-PET/CT showed that UC-MSC treatment in both high and low doses markedly ameliorated the left ventricle (LV) infarct area but did not significantly improve the myocardial perfusion defect. LV remodeling was inhibited by UC-MSC therapy, as reflected by a marked reduction in rthe fibrosis area at basal, middle, and apical levels and reduced extracellular matrix deposition in the total myocardial area. Inflammatory biomarkers (tumor necrosis factor alpha and interleukin-6) were reduced and pro-angiogenesis factors (vascular endothelial growth factor and platelet/endothelial cell adhesion molecule 1) were augmented in the myocardial infarct and border area. High-dose UC-MSCs increased the connexin 43 (Cx43) (myocardium preservation) expression in remote area of the LV myocardium after AMI. Conclusions Intravenous injection of UC-MSCs is a feasible and effective way to preserve LV function and ameliorate myocardial remodeling in porcine AMI. The cardioprotective effects of UC-MSCs were attributed to paracrine factors that appear to augment angiogenesis, limit inflammation, and preserve Cx43 gap junction. |
| first_indexed | 2024-12-12T03:28:46Z |
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| id | doaj.art-70b7043a16414c509d51b831e73616e6 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T03:28:46Z |
| publishDate | 2018-05-01 |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-70b7043a16414c509d51b831e73616e62022-12-22T00:39:58ZengBMCStem Cell Research & Therapy1757-65122018-05-019111710.1186/s13287-018-0888-zIntravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarctionMeikuang Lim0Weiqiang Wang1Lu Liang2Zhi-bo Han3Zongjin Li4Jie Geng5Meng Zhao6Honghong Jia7Jie Feng8Zhe Wei9Baoquan Song10Jiemin Zhang11Jun Li12Tianwen Liu13Fan Wang14Ting Li15Jianming Li16Yihu Fang17Jianhua Gao18Zhongchao Han19National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdBeijing Institute of Stem Cells, Health & Biotech Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdBeijing Institute of Stem Cells, Health & Biotech Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdState Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAnimal Medical Experiment Center, TEDA International Cardiovascular HospitalAnimal Medical Experiment Center, TEDA International Cardiovascular HospitalAnimal Medical Experiment Center, TEDA International Cardiovascular HospitalAnimal Medical Experiment Center, TEDA International Cardiovascular HospitalNuclear Medicine Department, TEDA International Cardiovascular HospitalNuclear Medicine Department, TEDA International Cardiovascular HospitalInstitute of Stem Cell, Jiangxi Medical CollegeInstitute of Stem Cell, Jiangxi Medical CollegeNational Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., LtdAbstract Background Multipotent mesenchymal stromal cell (MSC) therapy has been widely recognized as a feasible strategy for regenerating injured myocardial tissue. However, little is known about the efficacy of intravenous injection of allogeneic umbilical cord (UC) MSCs in preclinical models of porcine myocardial infarction. Methods Different dosages of allogeneic UC-MSCs or the vehicle [phosphate-buffered saline (PBS)] were delivered intravenously into an acute myocardial infarction (AMI) porcine model twice after coronary ligation. Echocardiography was performed to examine the cardiac function and single photon emission computed tomography (SPECT) and positron emission tomography (PET)/computed tomography (CT) was performed to detect cardiac perfusion and nonviable myocardium. At the end of the experiment, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Masson T staining were performed to determine the infarct area. The protein and gene expression levels associated with cardiac function, inflammation, and angiogenesis were examined by Western blot and real time polymerase chain reaction (PCR). In vivo trafficking of intravenous injection of allogeneic UC-MSCs enhanced green fluorescent protein (eGFP) was detected by real time PCR and immunofluorescence. Results After systemic delivery, allogeneic UC-MSCs were largely distributed in the lungs and some in the infracted myocardium. At week 8 following AMI, echocardiography demonstrated significantly improved fractional shortening in the high-dose (1.5 × 106 cells/kg) group. SPECT-PET/CT showed that UC-MSC treatment in both high and low doses markedly ameliorated the left ventricle (LV) infarct area but did not significantly improve the myocardial perfusion defect. LV remodeling was inhibited by UC-MSC therapy, as reflected by a marked reduction in rthe fibrosis area at basal, middle, and apical levels and reduced extracellular matrix deposition in the total myocardial area. Inflammatory biomarkers (tumor necrosis factor alpha and interleukin-6) were reduced and pro-angiogenesis factors (vascular endothelial growth factor and platelet/endothelial cell adhesion molecule 1) were augmented in the myocardial infarct and border area. High-dose UC-MSCs increased the connexin 43 (Cx43) (myocardium preservation) expression in remote area of the LV myocardium after AMI. Conclusions Intravenous injection of UC-MSCs is a feasible and effective way to preserve LV function and ameliorate myocardial remodeling in porcine AMI. The cardioprotective effects of UC-MSCs were attributed to paracrine factors that appear to augment angiogenesis, limit inflammation, and preserve Cx43 gap junction.http://link.springer.com/article/10.1186/s13287-018-0888-zUmbilical cordMultipotent mesenchymal stromal cellPorcineAcute myocardial infarction |
| spellingShingle | Meikuang Lim Weiqiang Wang Lu Liang Zhi-bo Han Zongjin Li Jie Geng Meng Zhao Honghong Jia Jie Feng Zhe Wei Baoquan Song Jiemin Zhang Jun Li Tianwen Liu Fan Wang Ting Li Jianming Li Yihu Fang Jianhua Gao Zhongchao Han Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction Stem Cell Research & Therapy Umbilical cord Multipotent mesenchymal stromal cell Porcine Acute myocardial infarction |
| title | Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| title_full | Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| title_fullStr | Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| title_full_unstemmed | Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| title_short | Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| title_sort | intravenous injection of allogeneic umbilical cord derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction |
| topic | Umbilical cord Multipotent mesenchymal stromal cell Porcine Acute myocardial infarction |
| url | http://link.springer.com/article/10.1186/s13287-018-0888-z |
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