Journal Article

Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction

Kishino, Yoshikazu, Seki, Tomohisa, Fukuda, Keiichi, Tamura, Noriko, Fujita, Jun, Kanazawa, Hideaki, Matsui, Makoto, Sano, Motoaki, Hirano, Akinori, Goto, Shinya, Okada, Marina, Nakajima, Kazuaki, Tabata, Yasuhiko, Tohyama, Shugo, Tabei, Ryota

2015

Overview

Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac function with a direct contraction effect and enhanced angiogenesis.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Angiogenesis / Animals / Biodegradability / Biodegradation / Biological products / Biomaterials / Biomedical materials / Cardiology / Cardiomyocytes / Cell Adhesion - drug effects / Clinical trials / Collagen / Contraction / Cytokines / Cytokines - metabolism / Drug dosages / Echocardiography / Female / Fetuses / Fibroblast growth factor 2 / Fibroblast growth factors / Fibroblasts / Gelatin / Gelatin - pharmacology / Gelatin - therapeutic use / Growth hormone / Heart / Heart attack / Heart attacks / Heart diseases / Heart failure / Heart Function Tests - drug effects / Heart transplantation / Heart transplants / Hepatocyte growth factor / Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology / Hydrogel, Polyethylene Glycol Dimethacrylate - therapeutic use / Hydrogels / Ischemia / Medicine / Myocardial infarction / Myocardial Infarction - physiopathology / Myocardial Infarction - therapy / Myocardium / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - transplantation / Neovascularization, Physiologic - drug effects / Ostomy / Phosphates / Platelets / Polymerase chain reaction / Polymers / Rats / Rats, Inbred Lew / Rats, Nude / Rodents / Science / Stem cells / Therapy / Thrombosis - pathology / Tissue engineering / Transplantation / Vascular endothelial growth factor / Water soluble polymers