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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 at early time points post-MI decreases infarct size.(A) Representative images of fresh heart sections from the apex to the mid-ventricle from each group. Arrows indicate the infarcted area (scale bar = 3 cm). (B) Statistical analysis of infarct size and (C) infarct length. Data are presented as the mean±SEM. *P<0.05, ***P<0.001.
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pone.0115430.g004: NF/MNC injection at early time points post-MI decreases infarct size.(A) Representative images of fresh heart sections from the apex to the mid-ventricle from each group. Arrows indicate the infarcted area (scale bar = 3 cm). (B) Statistical analysis of infarct size and (C) infarct length. Data are presented as the mean±SEM. *P<0.05, ***P<0.001.

Mentions: We collected heart tissues from each group 2 months post-MI and sectioned the hearts into 5 portions from the apex to mid-LV (Fig. 4A).We found that the infarct size in the MI+NF/MNC-1D group was smaller than the infarct sizes in the MI+NS, MI+NF-1D, MI+MNC-1D, and MI+NF/MNC-7D groups (Fig. 4B). We also measured the infarct length ratio (%) and obtained similar patterns to the changes in infarct size over time. The infarct length ratio of the 1 day post-MI group was significantly smaller than the 4 or 7 days group (Fig. 4C). While the difference is not significant, infarct length ratio from the 4 days group is smaller than the 7 days group (Fig. 4C). These results display a similar pattern with respect to cardiac functions. We further assessed the interstitial fibrosis at the remote area using trichrome staining (Fig. 5A). Not surprisingly, the injection of NF/MNC at 1 or 4 days post-MI resulted in significantly less collagen deposition. In contrast, collagen level increased significantly after the NF/MNC treatment at 7 days post-MI (Fig. 5B). Likewise, the fibrosis formation at the border area decreased significantly in the MI+NF/MNC-1D and-4D groups, but not in MI+NF/MNC-7D group (S1 Fig.). Together, these results indicate a strong correlation between a delayed NF/MNC treatment time and infarct size as well as cardiac fibrosis after MI.


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 at early time points post-MI decreases infarct size.(A) Representative images of fresh heart sections from the apex to the mid-ventricle from each group. Arrows indicate the infarcted area (scale bar = 3 cm). (B) Statistical analysis of infarct size and (C) infarct length. Data are presented as the mean±SEM. *P<0.05, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0115430.g004: NF/MNC injection at early time points post-MI decreases infarct size.(A) Representative images of fresh heart sections from the apex to the mid-ventricle from each group. Arrows indicate the infarcted area (scale bar = 3 cm). (B) Statistical analysis of infarct size and (C) infarct length. Data are presented as the mean±SEM. *P<0.05, ***P<0.001.
Mentions: We collected heart tissues from each group 2 months post-MI and sectioned the hearts into 5 portions from the apex to mid-LV (Fig. 4A).We found that the infarct size in the MI+NF/MNC-1D group was smaller than the infarct sizes in the MI+NS, MI+NF-1D, MI+MNC-1D, and MI+NF/MNC-7D groups (Fig. 4B). We also measured the infarct length ratio (%) and obtained similar patterns to the changes in infarct size over time. The infarct length ratio of the 1 day post-MI group was significantly smaller than the 4 or 7 days group (Fig. 4C). While the difference is not significant, infarct length ratio from the 4 days group is smaller than the 7 days group (Fig. 4C). These results display a similar pattern with respect to cardiac functions. We further assessed the interstitial fibrosis at the remote area using trichrome staining (Fig. 5A). Not surprisingly, the injection of NF/MNC at 1 or 4 days post-MI resulted in significantly less collagen deposition. In contrast, collagen level increased significantly after the NF/MNC treatment at 7 days post-MI (Fig. 5B). Likewise, the fibrosis formation at the border area decreased significantly in the MI+NF/MNC-1D and-4D groups, but not in MI+NF/MNC-7D group (S1 Fig.). Together, these results indicate a strong correlation between a delayed NF/MNC treatment time and infarct size as well as cardiac fibrosis after MI.

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