A novel approach to therapeutic angiogenesis for patients with critical limb ischemia by sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel - An initial report of the phase I-IIa study

Akira Marui, Yasuhiko Tabata, Shinsuke Kojima, Masaya Yamamoto, Keiichi Tambara, Takeshi Nishina, Yoshiaki Saji, Ken Ichi Inui, Tohru Hashida, Sumiko Yokoyama, Rie Onodera, Tadashi Ikeda, Masanori Fukushima, Masashi Komeda

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100 Citations (Scopus)

Abstract

Background: Limb ischemia remains a challenge. To overcome shortcomings or limitations of gene therapy or cell transplantation, a sustained release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel has been developed. Methods and Results: A phase I-IIa study was performed, in which 7 patients had critical limb ischemia. They were intramuscularly injected with 200μ g of bFGF-incorporated gelatin hydrogel microspheres into the gastrocnemius of the ischemic limb. End-points were safety and feasibility of treatment after 4 and 24 weeks. One patient was excluded from the study for social reasons, but only after symptomatic improvements. In the evaluation of the other 6 patients, significant improvements were observed in the distance walked in 6 min (295±42m vs 491±85m for pretreatment vs after 24 weeks, p=0.023) and in transcutaneous oxygen pressure (53.5±5.2 mmHg vs 65.5±4.0 mmHg, p=0.03). The rest pain scale also improved (3.5±0.2 vs 1.0±0.6, p=0.022). The ankle-brachial pressure index improved at 4 weeks but not at 24 weeks. Among 5 patients who had a non-healing foot ulcer, the ulcer was completely healed in 3 patients, reduced in 1, and there was no change in 1 patient at 24 weeks. The blood levels of bFGF were undetected or within the normal level in all patients. Conclusions: The sustained release of bFGF from gelatin hydrogel might be simple, safe, and effective to achieve therapeutic angiogenesis because it did not need genetic materials or collection of implanted cells, and because it did not have any general effects, which was supported by there being no elevation of the bFGF serum level.

Original languageEnglish
Pages (from-to)1181-1186
Number of pages6
JournalCirculation Journal
Volume71
Issue number8
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Angiogenesis
  • Basic fibroblast growth factor
  • Limb ischemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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