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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

Acute myocardial infarction changes bone marrow cell composition and decreases endothelial differentiation capability.(A) CD14 positive cells increased at day 1 post-MI while the CD16 positive cell decreased at day 4 and day 7 after infarction in B with n ≥3 per groups. *P <0.05. (C) Representative images of DiI fluorescence (red) overlapped with immunostaining for von Willebrand factor (vWF, green) from different groups. Nuclei were stained using DAPI (blue). (D) Quantification of the ratio of cells stained positively with vWF. Data are presented as the mean±SEM. *P<0.05. Scale bar = 50 μm.
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pone.0115430.g008: Acute myocardial infarction changes bone marrow cell composition and decreases endothelial differentiation capability.(A) CD14 positive cells increased at day 1 post-MI while the CD16 positive cell decreased at day 4 and day 7 after infarction in B with n ≥3 per groups. *P <0.05. (C) Representative images of DiI fluorescence (red) overlapped with immunostaining for von Willebrand factor (vWF, green) from different groups. Nuclei were stained using DAPI (blue). (D) Quantification of the ratio of cells stained positively with vWF. Data are presented as the mean±SEM. *P<0.05. Scale bar = 50 μm.

Mentions: Since the MNCs administered to the MI porcine models were extracted from the same animals after MI, the effect of MI on the bone marrow cell composition was analyzed. Bone marrow samples were taken at 1, 4, and 7 days post-MI. The number of cells that stained positively for CD14 and CD16 were examined (Fig. 8A and 8B). The percentage of CD14+ cells increased at 1 day post-MI, and then decreased to the similar level as the sham group at 4 and 7 days. In contrast, CD16+ cells showed a decreasing trend from 1 to 7 days post-MI. The ability of MNC differentiation into vascular cells was also examined. It was noticed that the MNCs administered at 1 day post-MI showed the greatest rate of differentiation into endothelial cells compared to those injected at 4 and 7 days (Fig. 8C, D and S4 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)

Acute myocardial infarction changes bone marrow cell composition and decreases endothelial differentiation capability.(A) CD14 positive cells increased at day 1 post-MI while the CD16 positive cell decreased at day 4 and day 7 after infarction in B with n ≥3 per groups. *P <0.05. (C) Representative images of DiI fluorescence (red) overlapped with immunostaining for von Willebrand factor (vWF, green) from different groups. Nuclei were stained using DAPI (blue). (D) Quantification of the ratio of cells stained positively with vWF. Data are presented as the mean±SEM. *P<0.05. Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0115430.g008: Acute myocardial infarction changes bone marrow cell composition and decreases endothelial differentiation capability.(A) CD14 positive cells increased at day 1 post-MI while the CD16 positive cell decreased at day 4 and day 7 after infarction in B with n ≥3 per groups. *P <0.05. (C) Representative images of DiI fluorescence (red) overlapped with immunostaining for von Willebrand factor (vWF, green) from different groups. Nuclei were stained using DAPI (blue). (D) Quantification of the ratio of cells stained positively with vWF. Data are presented as the mean±SEM. *P<0.05. Scale bar = 50 μm.
Mentions: Since the MNCs administered to the MI porcine models were extracted from the same animals after MI, the effect of MI on the bone marrow cell composition was analyzed. Bone marrow samples were taken at 1, 4, and 7 days post-MI. The number of cells that stained positively for CD14 and CD16 were examined (Fig. 8A and 8B). The percentage of CD14+ cells increased at 1 day post-MI, and then decreased to the similar level as the sham group at 4 and 7 days. In contrast, CD16+ cells showed a decreasing trend from 1 to 7 days post-MI. The ability of MNC differentiation into vascular cells was also examined. It was noticed that the MNCs administered at 1 day post-MI showed the greatest rate of differentiation into endothelial cells compared to those injected at 4 and 7 days (Fig. 8C, D and S4 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