Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation

Sakakibara, Yutaka; Nishimura, Kazunobu; Tambara, Keiichi; Yamamoto, Masaya; Lu, Fanglin; Tabata, Yasuhiko; Komeda, Masashi

doi:10.1067/mtc.2002.121293

Cited by 136 publications

(98 citation statements)

References 23 publications

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“…The angiogenic effect of bFGF has been widely utilized to stimulate blood vessel formation in vivo to improve the function of diseased tissue or increase the survival of transplanted cells by enhanced nutrient transport [5,29,30]. A drug delivery system is often employed to deliver bioactive bFGF over a prolonged period at the target site since bFGF has a short half-life in vivo.…”

Section: Discussionmentioning

confidence: 99%

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

Guan

Stankus

Wagner

2007

Journal of Controlled Release

149

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Scaffolds that better approximate the mechanical properties of cardiovascular and other soft tissues might provide a more appropriate mechanical environment for tissue development or healing in vivo. An ability to induce local angiogenesis by controlled release of an angiogenic factor, such as basic fibroblast growth factor (bFGF), from a biodegradable scaffold with mechanical properties more closely approximating soft tissue could find application in a variety of settings. Toward this end biodegradable poly(ester urethane)urea (PEUU) scaffolds loaded with bFGF were fabricated by thermally induced phase separation. Scaffold morphology, mechanical properties, release kinetics, hydrolytic degradation and bioactivity of the released bFGF were assessed. The scaffolds had interconnected pores with porosities of 90% or greater and pore sizes ranging from 34-173 μm. Scaffolds had tensile strengths of 0.25-2.8 MPa and elongations at break of 81-443%. Incorporation of heparin into the scaffold increased the initial burst release of bFGF, while the initial bFGF loading content did not change release kinetics significantly. The released bFGF remained bioactive over 21 days as assessed by smooth muscle mitogenicity. Scaffolds loaded with bFGF showed slightly higher degradation rates than unloaded control scaffolds. Smooth muscle cells seeded into the scaffolds with bFGF showed higher cell densities than for control scaffolds after 7 days of culture. The bFGFreleasing PEUU scaffolds thus exhibited a combination of mechanical properties and bioactivity that might be attractive for use in cardiovascular and other soft tissue applications.

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Section: Discussionmentioning

confidence: 99%

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

Guan

Stankus

Wagner

2007

Journal of Controlled Release

149

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“…Sustained release of fibroblast growth factor (FGF) from injectable hydrogels has been extensively explored to stimulate angiogenesis following MI [85][86][87][88][89][90]. FGF is a powerful angiogenic molecule, but has a very short half-life in vivo.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Injectable Acellular Hydrogels for Cardiac Repair

Tous

Purcell

Ifkovits

et al. 2011

J. of Cardiovasc. Trans. Res.

152

136

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Injectable hydrogels are being developed as potential translatable materials to influence the cascade of events that occur after myocardial infarction. These hydrogels, consisting of both synthetic and natural materials, form through numerous chemical crosslinking and assembly mechanisms and can be used as bulking agents or for the delivery of biological molecules. Specifically, a range of materials are being applied that alter the resulting mechanical and biological signals after infarction and have shown success in reducing stresses in the myocardium and limiting the resulting adverse left ventricular (LV) remodeling. Additionally, the delivery of molecules from injectable hydrogels can influence cellular processes such as apoptosis and angiogenesis in cardiac tissue or can be used to recruit stem cells for repair. There is still considerable work to be performed to elucidate the mechanisms of these injectable hydrogels and to optimize their various properties (e.g., mechanics and degradation profiles). Furthermore, although the experimental findings completed to date in small animals are promising, future work needs to focus on the use of large animal models in clinically relevant scenarios. Interest in this therapeutic approach is high due to the potential for developing percutaneous therapies to limit LV remodeling and to prevent the onset of congestive heart failure that occurs with loss of global LV function. This review focuses on recent efforts to develop these injectable and acellular hydrogels to aid in cardiac repair.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Among various types of cell sources, skeletal myoblasts (SM) have drawn our attentions because of their clinical applicability and regenerative capacity. 6 -15 To date, several clinical trials of skeletal myoblast transplantation are under way in patients with chronically ischemic hearts that are not suitable for standard myocardial revascularization.…”

mentioning

confidence: 99%

Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers

Tambara

Sakakibara²,

Sakaguchi³

et al. 2003

Circulation

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Background-It is not clear how many skeletal myoblsts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling. Methods and Results-MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (nϭ15), 5ϫ10 7 ; group II (nϭ15), 5ϫ10 6 ; and group III (nϭ15), 5ϫ10 5 cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes. Results-Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm 3 . In the other groups, FSMHC-positive cells were found only partly in the MI area.

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Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation

Abstract: Prevascularization with basic fibroblast growth factor-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. We expect that this system will contribute to regeneration medicine through its extensive application to other growth factors.

Cited by 136 publications

References 23 publications

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

Injectable Acellular Hydrogels for Cardiac Repair

Transplanted Skeletal Myoblasts Can Fully Replace the Infarcted Myocardium When They Survive in the Host in Large Numbers

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