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The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.

Chang MY, Chang CH, Chen CH, Cheng B, Lin YD, Luo CY, Wu HL, Yang YJ, Chen JH, Hsieh PC - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.

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).

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.

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Related in: MedlinePlus

NF/MNC injection increases transplant cell retention after MI.(A) Representative DiI+ MNC (red) after injection with or without NF at 1, 4, and 7 days post-infarction. Nuclei were stained using DAPI. (B) The statistics of DiI+ MNC retention ratio. Data are presented as the mean±SEM. *P<0.05, ***P<0.001. Scale bar = 100 μm.
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pone.0115430.g006: NF/MNC injection increases transplant cell retention after MI.(A) Representative DiI+ MNC (red) after injection with or without NF at 1, 4, and 7 days post-infarction. Nuclei were stained using DAPI. (B) The statistics of DiI+ MNC retention ratio. Data are presented as the mean±SEM. *P<0.05, ***P<0.001. Scale bar = 100 μm.

Mentions: Cell retention is one of the major determining factors for effective and successful cell transplantation. Therefore, we compared the amount of cells retained 2 months post-MI for each of the injection groups (Fig. 6A). We found that the injection of NF/MNC significantly increased MNC retention even at 2 months post-MI compared with the injection of MNC alone (Fig. 6B). Interestingly, although the retention ratio exhibited a decreasing trend with time, there was no significant difference among the different injection time points (Fig. 6B). These results were further confirmed by confocal microscopy showing co-localization of the Dil and DAPI staining (S2 Fig.).


The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.

Chang MY, Chang CH, Chen CH, Cheng B, Lin YD, Luo CY, Wu HL, Yang YJ, Chen JH, Hsieh PC - PLoS ONE (2015)

NF/MNC injection increases transplant cell retention after MI.(A) Representative DiI+ MNC (red) after injection with or without NF at 1, 4, and 7 days post-infarction. Nuclei were stained using DAPI. (B) The statistics of DiI+ MNC retention ratio. Data are presented as the mean±SEM. *P<0.05, ***P<0.001. Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355625&req=5

pone.0115430.g006: NF/MNC injection increases transplant cell retention after MI.(A) Representative DiI+ MNC (red) after injection with or without NF at 1, 4, and 7 days post-infarction. Nuclei were stained using DAPI. (B) The statistics of DiI+ MNC retention ratio. Data are presented as the mean±SEM. *P<0.05, ***P<0.001. Scale bar = 100 μm.
Mentions: Cell retention is one of the major determining factors for effective and successful cell transplantation. Therefore, we compared the amount of cells retained 2 months post-MI for each of the injection groups (Fig. 6A). We found that the injection of NF/MNC significantly increased MNC retention even at 2 months post-MI compared with the injection of MNC alone (Fig. 6B). Interestingly, although the retention ratio exhibited a decreasing trend with time, there was no significant difference among the different injection time points (Fig. 6B). These results were further confirmed by confocal microscopy showing co-localization of the Dil and DAPI staining (S2 Fig.).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.

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).

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.

Show MeSH
Related in: MedlinePlus