Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects.
Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.|Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Min
M
Cai
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Rui
R
Shen
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Lei
L
Song
Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Minjie
M
Lu
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Jianguang
J
Wang
Department of Nuclear Medicine, Shanxi Provincial People's Hospital, Taiyuan, China.
Shihua
S
Zhao
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Yue
Y
Tang
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Xianmin
X
Meng
Department of Pathophysiology, Nankai University School of Medicine, Tianjin, China.
Zongjin
Z
Li
Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center of Cardiovascular Disease, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.
Zuo-Xiang
ZX
He
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000072078:Positron Emission Tomography Computed Tomography; D020127:Recovery of Function; D013552:Swine; D013556:Swine, Miniature