Key result
Peptide nanofibers plus bone marrow cells improve post-MI systolic function and boost cell retention ~8-fold.
Why the study?
Intramyocardial biomaterial injection improves post-MI cardiac function in rodents and cell therapy is hampered by poor retention of transplanted cells, motivating evaluation of whether self-assembling peptide nanofibers combined with autologous bone marrow mononuclear cells attenuate cardiac remodeling and dysfunction in a large-animal pig MI model.
Does intramyocardial injection of self-assembling peptide nanofibers combined with autologous bone marrow mononuclear cells improve cardiac function, ventricular remodeling, and cell retention in a pig model of myocardial infarction?
Does intramyocardial injection of self-assembling peptide nanofibers combined with autologous bone marrow mononuclear cells improve cardiac function, ventricular remodeling, and cell retention in a pig model of myocardial infarction?
In a porcine myocardial infarction model, combining intramyocardial self-assembling peptide nanofiber injection with autologous bone marrow mononuclear cells markedly enhanced cell retention, attenuated ventricular remodeling, and improved both systolic and diastolic cardiac function.
NF-MNC co-injection improves retention and function in porcine MI; leaves open clinical translation pending human trials.
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.
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Lin et al. (2010) studied Myocardial infarction (porcine model) (n=40). Intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with autologous bone marrow mononuclear cells (MNCs) vs. Normal saline (2 mL), NFs alone, MNCs alone, or sham was evaluated on Systolic and diastolic cardiac function (+dP/dt and -dP/dt) and transplanted cell retention at 28 days. Intramyocardial peptide nanofibers plus bone marrow cells improved +dP/dt (1693.7 vs 1214.5 mm Hg/s in saline) and cell retention (229.4 vs 29.3 cells/mm2) post-MI in pigs.
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