title: Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome.
abstract: Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.|Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Shen
authors.affiliation: Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Thomas George
authors.initials: TG
authors.lastname: Caranasos
authors.affiliation: The Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Zegen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Vandergriff
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Allen
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.
authors.forename: Michael Taylor
authors.initials: MT
authors.lastname: Hensley
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.
authors.forename: Phuong-Uyen
authors.initials: PU
authors.lastname: Dinh
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.
authors.forename: Jhon
authors.initials: J
authors.lastname: Cores
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
authors.affiliation: Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill &North Carolina State University, Chapel Hill and Raleigh, North Carolina 27599 and 27607, USA.|The Cyrus Tang Hematology Center, Soochow University, Suzhou, Jiangsu 215123, China.|Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000637:transplantation; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000378:metabolism* / Q000637:transplantation; D017077:Culture Media, Conditioned / Q000737:chemistry* / Q000302:isolation & purification; D004195:Disease Models, Animal; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015552:Injections, Intralesional; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication; D020127:Recovery of Function / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C553307:HGF protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C519530:insulin-like growth factor-1, mouse; C467480:vascular endothelial growth factor A, mouse; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I