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Enhancing retention and efficacy of cardiosphere-derived cells administered after myocardial infarction using a hyaluronan-gelatin hydrogel.

ABSTRACT: Cardiosphere-derived cells (CDCs) are under clinical development and are currently being tested in a clinical trial enrolling patients who have undergone a myocardial infarction. CDCs are presently administered via infusion into the infarct-related artery and have been shown in early clinical trials to be effective agents of myocardial regeneration. This review describes the administration of CDCs in a hyaluronan-gelatin hydrogel via myocardial injection and the subsequent improvements in therapeutic benefit seen in animal models. Development of a next generation therapy involving the combination of CDCs and hydrogel is discussed.

SUBMITTER: Smith RR

PROVIDER: S-EPMC3732325 | biostudies-literature | 2013 Jan-Mar

REPOSITORIES: biostudies-literature

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Enhancing retention and efficacy of cardiosphere-derived cells administered after myocardial infarction using a hyaluronan-gelatin hydrogel.

Smith Rachel Ruckdeschel RR Marbán Eduardo E Marbán Linda L

Biomatter 20130101 1

Cardiosphere-derived cells (CDCs) are under clinical development and are currently being tested in a clinical trial enrolling patients who have undergone a myocardial infarction. CDCs are presently administered via infusion into the infarct-related artery and have been shown in early clinical trials to be effective agents of myocardial regeneration. This review describes the administration of CDCs in a hyaluronan-gelatin hydrogel via myocardial injection and the subsequent improvements in therap ...[more]

PMID: 23538511

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Project description: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.

Dataset Information

Enhancing retention and efficacy of cardiosphere-derived cells administered after myocardial infarction using a hyaluronan-gelatin hydrogel.

Publications

Enhancing retention and efficacy of cardiosphere-derived cells administered after myocardial infarction using a hyaluronan-gelatin hydrogel.

Similar Datasets

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