title: Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: 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.).
authors.forename: Junnan
authors.initials: J
authors.lastname: Tang
authors.affiliation: 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.).
authors.forename: Kodai
authors.initials: K
authors.lastname: Nishi
authors.affiliation: 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.).
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: 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.).
authors.forename: Phuong-Uyen
authors.initials: PU
authors.lastname: Dinh
authors.affiliation: 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.).
authors.forename: Jhon
authors.initials: J
authors.lastname: Cores
authors.affiliation: 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.).
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.affiliation: 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.).
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.).
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D049268:Positron-Emission Tomography / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: artificial cells; mesenchymal stem cells; myocardial infarction; regeneration; stem cells; tissue engineering