title: Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.
abstract: 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.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsui
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Tohyama
authors.affiliation: Department of Medicine (Cardiology), Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tamura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kanazawa
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kishino
authors.affiliation: Department of Cardiovascular Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tabei
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.affiliation: Department of Medicine (Cardiology), Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000494:pharmacology / Q000627:therapeutic use*; D006334:Heart Function Tests / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000637:transplantation*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D013927:Thrombosis / Q000473:pathology
chemical_list: D016207:Cytokines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin