Lan Luo1, Junnan Tang1, Kodai Nishi1, Chen Yan1, Phuong-Uyen Dinh1, Jhon Cores1, Takashi Kudo1, Jinying Zhang1, Tao-Sheng Li1, Ke Cheng2. 1. From the Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Japan (L.L., C.Y., T.-S.L.); Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, Japan (K.N., T.K.); Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan, China (J.T., J.Z.); Department of Molecular Biomedical Sciences and Comparative Medicine Institute (J.T., P.-U.D., J.C., K.C.) and Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh (J.T., P.-U.D., J.C., K.C.); and Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (K.C.). 2. From the Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Japan (L.L., C.Y., T.-S.L.); Department of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, Japan (K.N., T.K.); Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan, China (J.T., J.Z.); Department of Molecular Biomedical Sciences and Comparative Medicine Institute (J.T., P.-U.D., J.C., K.C.) and Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh (J.T., P.-U.D., J.C., K.C.); and Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (K.C.). ke_cheng@ncsu.edu litaoshe@nagasaki-u.ac.jp.
Abstract
RATIONALE: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. OBJECTIVE: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. METHODS AND RESULTS: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. CONCLUSIONS: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
RATIONALE: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. OBJECTIVE: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. METHODS AND RESULTS: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. CONCLUSIONS: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
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