Gelatin Hydrogel enhances the engraftment of transplanted Cardiomyocytes and angiogenesis to ameliorate cardiac function after myocardial infarction

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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<inf>6</inf> or 1x10<inf>6</inf> 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<inf>6</inf> 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.

Original languageEnglish
Article numbere0133308
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - 2015 Jul 17

Fingerprint

Hydrogel
myocardial infarction
hydrocolloids
cardiac output
Gelatin
angiogenesis
gelatin
Cardiac Myocytes
Myocardial Infarction
Transplantation
Phosphates
phosphates
Echocardiography
echocardiography
Heart Transplantation
Cell- and Tissue-Based Therapy
myocardium
cardiomyocytes
collagen
Rats

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gelatin Hydrogel enhances the engraftment of transplanted Cardiomyocytes and angiogenesis to ameliorate cardiac function after myocardial infarction. / Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi.

In: PLoS One, Vol. 10, No. 7, e0133308, 17.07.2015.

Research output: Contribution to journalArticle

Nakajima, Kazuaki ; Fujita, Jun ; Matsui, Makoto ; Tohyama, Shugo ; Tamura, Noriko ; Kanazawa, Hideaki ; Seki, Tomohisa ; Kishino, Yoshikazu ; Hirano, Akinori ; Okada, Marina ; Tabei, Ryota ; Sano, Motoaki ; Goto, Shinya ; Tabata, Yasuhiko ; Fukuda, Keiichi. / Gelatin Hydrogel enhances the engraftment of transplanted Cardiomyocytes and angiogenesis to ameliorate cardiac function after myocardial infarction. In: PLoS One. 2015 ; Vol. 10, No. 7.
@article{272ad126ea59483a90082452cc3d0af9,
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 (5×106 or 1x106 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 5×106 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.",
author = "Kazuaki Nakajima and Jun Fujita and Makoto Matsui and Shugo Tohyama and Noriko Tamura and Hideaki Kanazawa and Tomohisa Seki and Yoshikazu Kishino and Akinori Hirano and Marina Okada and Ryota Tabei and Motoaki Sano and Shinya Goto and Yasuhiko Tabata and Keiichi Fukuda",
year = "2015",
month = "7",
day = "17",
doi = "10.1371/journal.pone.0133308",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Gelatin Hydrogel enhances the engraftment of transplanted Cardiomyocytes and angiogenesis to ameliorate cardiac function after myocardial infarction

AU - Nakajima, Kazuaki

AU - Fujita, Jun

AU - Matsui, Makoto

AU - Tohyama, Shugo

AU - Tamura, Noriko

AU - Kanazawa, Hideaki

AU - Seki, Tomohisa

AU - Kishino, Yoshikazu

AU - Hirano, Akinori

AU - Okada, Marina

AU - Tabei, Ryota

AU - Sano, Motoaki

AU - Goto, Shinya

AU - Tabata, Yasuhiko

AU - Fukuda, Keiichi

PY - 2015/7/17

Y1 - 2015/7/17

N2 - 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 (5×106 or 1x106 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 5×106 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.

AB - 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 (5×106 or 1x106 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 5×106 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.

UR - http://www.scopus.com/inward/record.url?scp=84941285518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941285518&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0133308

DO - 10.1371/journal.pone.0133308

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e0133308

ER -