PMID- 25757076 OWN - NLM STAT- MEDLINE DCOM- 20160113 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction. PG - e0115430 LID - 10.1371/journal.pone.0115430 [doi] LID - e0115430 AB - 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). METHODS AND 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. FAU - Chang, Ming-Yao AU - Chang MY AD - Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan. FAU - Chang, Chih-Han AU - Chang CH AD - Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan. FAU - Chen, Chien-Hsi AU - Chen CH AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. FAU - Cheng, Bill AU - Cheng B AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. FAU - Lin, Yi-Dong AU - Lin YD AD - Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. FAU - Luo, Chwan-Yau AU - Luo CY AD - Department of Surgery, National Cheng Kung University & Hospital, Tainan, Taiwan. FAU - Wu, Hua-Lin AU - Wu HL AD - Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan. FAU - Yang, Yu-Jen AU - Yang YJ AD - Department of Surgery, National Cheng Kung University & Hospital, Tainan, Taiwan. FAU - Chen, Jyh-Hong AU - Chen JH AD - Department of Internal Medicine, National Cheng Kung University & Hospital, Tainan, Taiwan. FAU - Hsieh, Patrick C H AU - Hsieh PC AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150310 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Peptides) SB - IM MH - Animals MH - Bone Marrow Transplantation MH - Cell Differentiation MH - Drug Administration Schedule MH - Endothelial Cells/physiology MH - Endothelium, Vascular/pathology MH - Myocardial Infarction/pathology/*therapy MH - Myocardium/pathology MH - Nanofibers/*therapeutic use MH - Peptides/therapeutic use MH - Swine MH - Swine, Miniature MH - Time Factors MH - Transplantation, Autologous MH - Ventricular Remodeling PMC - PMC4355625 COIS- Competing Interests: Patrick C.H. Hsieh has read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Patrick Hsieh received research support from Celgene Cellular Therapeutics and Meridigen Biotech Co. Although the authors had received research support from Celgene Cellular Therapeutics and Meridigen Biotech Co., this does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. EDAT- 2015/03/11 06:00 MHDA- 2016/01/14 06:00 PMCR- 2015/03/10 CRDT- 2015/03/11 06:00 PHST- 2014/09/14 00:00 [received] PHST- 2014/11/23 00:00 [accepted] PHST- 2015/03/11 06:00 [entrez] PHST- 2015/03/11 06:00 [pubmed] PHST- 2016/01/14 06:00 [medline] PHST- 2015/03/10 00:00 [pmc-release] AID - PONE-D-14-41355 [pii] AID - 10.1371/journal.pone.0115430 [doi] PST - epublish SO - PLoS One. 2015 Mar 10;10(3):e0115430. doi: 10.1371/journal.pone.0115430. eCollection 2015.