Journal Article

The Time Window for Therapy with Peptide Nanofibers Combined with Autologous Bone Marrow Cells in Pigs after Acute Myocardial Infarction

Chang, Chih-Han, Wu, Hua-Lin, Chen, Chien-Hsi, Luo, Chwan-Yau, Yang, Yu-Jen, Chang, Ming-Yao, Chen, Jyh-Hong, Hsieh, Patrick C. H., Cheng, Bill, Lin, Yi-Dong

2015

Overview

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). 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Anesthesia / Animals / Apoptosis / Autografts / Biomedical engineering / Bone marrow / Bone Marrow Transplantation / Cardiomyocytes / Cardiovascular disease / Care and treatment / Catheterization / Cell Differentiation / Collagen / Complications and side effects / Coronary artery / Coronary vessels / Drug Administration Schedule / Echocardiography / Endothelial Cells - physiology / Endothelium, Vascular - pathology / Engineering / Feasibility studies / Health aspects / Heart / Heart attack / Heart attacks / Heart cells / Hogs / Hospitals / Infarction / Injection / Laboratory animals / Leukocytes (mononuclear) / Myocardial infarction / Myocardial Infarction - pathology / Myocardial Infarction - therapy / Myocardium - pathology / Nanofibers / Nanofibers - therapeutic use / Peptides / Peptides - therapeutic use / Performance evaluation / Pigs / Retention / Surgery / Swine / Swine, Miniature / Therapy / Time Factors / Transplantation, Autologous / Ventricle / Ventricular Remodeling / Windows (intervals)