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J Thorac Cardiovasc Surg 2002;124:50-56
© 2002 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

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

Yutaka Sakakibara, MDa, Kazunobu Nishimura, MD, PhDa, Keiichi Tambara, MDa, Masaya Yamamoto, PhDb, Fanglin Lu, MDa, Yasuhiko Tabata, PhDb, Masashi Komeda, MD, PhDa

From the Department of Cardiovascular Surgery, Graduate School of Medicine,a Kyoto University, and the Institute for Frontier Medical Sciences,b Kyoto University, Kyoto, Japan.

This research was supported by a "Grant-in-Aid" for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology, and "Research for the Future" Program from the Japan Society for the Promotion of Science.

Received for publication Aug 27, 2001. Revisions requested Oct 3, 2001; revisions received Oct 25, 2001. Accepted for publication Oct 26, 2001. Address for reprints: Masashi Komeda, MD, PhD, Professor, Graduate School of Medicine, Department of Cardiovascular Surgery, Kyoto University, 54 Kawaharacho Shogoin Sakyo-ku, Kyoto, Japan, 606-8507 (E-mail: masakom{at}kuhp.kyoto-u.ac.jp).

Objective: The effects of cell transplantation on the ischemic failing heart have already been documented. However, the area in and around infarct regions is not a good environment for cells to survive in because they are exposed to poor conditions in which certain requirements cannot be adequately supplied. We therefore designed a study to investigate the efficacy of prevascularization in ischemic regions before cell transplantation.
Methods: Rats with myocardial infarction were randomized into 4 groups: 11 rats received a culture medium injection to the left ventricular wall (control group), 11 received fetal cardiomyocyte transplantation (TX group), 11 received gelatin hydrogel microspheres incorporating basic fibroblast growth factor (FGF group), and 11 received basic fibroblast growth factor pretreatment sequentially, followed by cardiomyocyte transplantation (FGF-TX group). Four weeks later, left ventricular function was assessed by means of echocardiography and cardiac catheterization.
Results: In the FGF and FGF-TX groups neovascularization was found in the scar tissue 1 week later. The TX, FGF, and FGF-TX groups showed better fractional shortening than the control group (TX, FGF, FGF-TX, and control: 28% ± 4.4%, 24% ± 8.6%, 27% ± 7.3%, and 17% ± 4.6%, respectively; P < .01). Left ventricular maximum time-varying elastance was higher in the FGF-TX group than in the TX and FGF groups (FGF-TX, TX, and FGF: 0.52 ± 0.23, 0.30 ± 0.08, and 0.27 ± 0.20 mm Hg/µL, respectively; P < .01). Histologically, more transplanted cells survived in the FGF-TX group than in the TX group.
Conclusions: 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.




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