Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs

Yi Dong Lin, Ming-Long Yeh, Yu Jen Yang, Da Ching Tsai, Ting Yu Chu, Ya Yun Shih, Min Yao Chang, Yen-Wen Liu, Alan C.L. Tang, Tsai-Yun Chen, Chwan-Yau Luo, Kung-Chao Chang, Jyh Hong Chen, Hua-Lin Wu, Tin Kan Hung, Patrick C.H. Hsieh

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Background-: Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and results-: A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and-dP/dt (1214.5±91.9 and-1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and-1809. 6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm 2 in MI+MNCs and 229.4±41.4 cells/mm 2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-: We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

Original languageEnglish
JournalCirculation
Volume122
Issue number11 SUPPL. 1
DOIs
Publication statusPublished - 2010 Sep 14

Fingerprint

Nanofibers
Ventricular Remodeling
Cell- and Tissue-Based Therapy
Bone Marrow Cells
Swine
Myocardial Infarction
Peptides
Injections
Miniature Swine
Coronary Occlusion
Biocompatible Materials
Therapeutic Uses

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lin, Yi Dong ; Yeh, Ming-Long ; Yang, Yu Jen ; Tsai, Da Ching ; Chu, Ting Yu ; Shih, Ya Yun ; Chang, Min Yao ; Liu, Yen-Wen ; Tang, Alan C.L. ; Chen, Tsai-Yun ; Luo, Chwan-Yau ; Chang, Kung-Chao ; Chen, Jyh Hong ; Wu, Hua-Lin ; Hung, Tin Kan ; Hsieh, Patrick C.H. / Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. In: Circulation. 2010 ; Vol. 122, No. 11 SUPPL. 1.
@article{cf29888cf4da4a7b8a4a2003d060580c,
title = "Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs",
abstract = "Background-: Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and results-: A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1{\%} NFs with or without 1×10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and-dP/dt (1214.5±91.9 and-1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and-1809. 6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm 2 in MI+MNCs and 229.4±41.4 cells/mm 2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-: We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.",
author = "Lin, {Yi Dong} and Ming-Long Yeh and Yang, {Yu Jen} and Tsai, {Da Ching} and Chu, {Ting Yu} and Shih, {Ya Yun} and Chang, {Min Yao} and Yen-Wen Liu and Tang, {Alan C.L.} and Tsai-Yun Chen and Chwan-Yau Luo and Kung-Chao Chang and Chen, {Jyh Hong} and Hua-Lin Wu and Hung, {Tin Kan} and Hsieh, {Patrick C.H.}",
year = "2010",
month = "9",
day = "14",
doi = "10.1161/CIRCULATIONAHA.110.939512",
language = "English",
volume = "122",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "11 SUPPL. 1",

}

Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. / Lin, Yi Dong; Yeh, Ming-Long; Yang, Yu Jen; Tsai, Da Ching; Chu, Ting Yu; Shih, Ya Yun; Chang, Min Yao; Liu, Yen-Wen; Tang, Alan C.L.; Chen, Tsai-Yun; Luo, Chwan-Yau; Chang, Kung-Chao; Chen, Jyh Hong; Wu, Hua-Lin; Hung, Tin Kan; Hsieh, Patrick C.H.

In: Circulation, Vol. 122, No. 11 SUPPL. 1, 14.09.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs

AU - Lin, Yi Dong

AU - Yeh, Ming-Long

AU - Yang, Yu Jen

AU - Tsai, Da Ching

AU - Chu, Ting Yu

AU - Shih, Ya Yun

AU - Chang, Min Yao

AU - Liu, Yen-Wen

AU - Tang, Alan C.L.

AU - Chen, Tsai-Yun

AU - Luo, Chwan-Yau

AU - Chang, Kung-Chao

AU - Chen, Jyh Hong

AU - Wu, Hua-Lin

AU - Hung, Tin Kan

AU - Hsieh, Patrick C.H.

PY - 2010/9/14

Y1 - 2010/9/14

N2 - Background-: Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and results-: A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and-dP/dt (1214.5±91.9 and-1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and-1809. 6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm 2 in MI+MNCs and 229.4±41.4 cells/mm 2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-: We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

AB - Background-: Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and results-: A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and-dP/dt (1214.5±91.9 and-1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and-1809. 6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm 2 in MI+MNCs and 229.4±41.4 cells/mm 2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-: We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

UR - http://www.scopus.com/inward/record.url?scp=77957239764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957239764&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.110.939512

DO - 10.1161/CIRCULATIONAHA.110.939512

M3 - Article

C2 - 20837904

AN - SCOPUS:77957239764

VL - 122

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 11 SUPPL. 1

ER -