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


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.
Lin
Yi-Dong
YD
Institute of Biomedical Engineering, National Cheng Kung University & Hospital, Tainan, Taiwan.
Yeh
Ming-Long
ML
Yang
Yu-Jen
YJ
Tsai
Da-Ching
DC
Chu
Ting-Yu
TY
Shih
Ya-Yun
YY
Chang
Min-Yao
MY
Liu
Yen-Wen
YW
Tang
Alan C L
AC
Chen
Tsai-Yun
TY
Luo
Chwan-Yau
CY
Chang
Kung-Chao
KC
Chen
Jyh-Hong
JH
Wu
Hua-Lin
HL
Hung
Tin-Kan
TK
Hsieh
Patrick C H
PC
D000818:Animals; D016026:Bone Marrow Transplantation; D006801:Humans; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D057139:Nanofibers / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling / Q000187:drug effects*
D010455:Peptides