title: The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.
abstract: BACKGROUND
  We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI).
  
  
  RESULTS
  A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs.
  
  
  CONCLUSIONS
  Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Han
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Hsi
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Bill
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Lin
authors.affiliation: Department of Surgery, National Cheng Kung University & Hospital, Tainan, Taiwan.
authors.forename: Chwan-Yau
authors.initials: CY
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
authors.affiliation: Department of Surgery, National Cheng Kung University & Hospital, Tainan, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, National Cheng Kung University & Hospital, Tainan, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Surgery, National Cheng Kung University & Hospital, Tainan, Taiwan.
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D004334:Drug Administration Schedule; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D057139:Nanofibers / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling
chemical_list: D010455:Peptides