Therapeutic angiogenesis by the controlled release of basic fibroblast growth factor for ischemic limb and heart injury: toward safety and minimal invasiveness.
We review our studies on therapeutic angiogenesis using basic fibroblast growth factor (bFGF) released in a controlled manner from biodegradable gelatin hydrogel (GH). The bFGF-GH was intramuscularly injected in rabbits with limb ischemia. The group treated with bFGF showed an increase in tissue blood flow under laser Doppler imaging and histology showed a greater vascular density compared with controls. Also, bFGF-GH was subepicardially injected into old heart infarcts in rats. In the group treated with bFGF, improved left ventricular function was shown by echocardiography and cardiac catheterization, increased regional blood flow in the peri-infarct area was detected by pinhole single-photon emission computed tomography using (201)Tl, and increased vascular density was demonstrated by histology. In rabbits with acute myocardial infarction, the heart was wrapped with the omentum (including the gastroepiploic artery) and a bFGF-GH sheet was applied. Postoperative assessment revealed rich communication from the gastroepiploic artery to the coronary artery and improved cardiac function. The controlled release of bFGF was effective for both limb and heart ischemia and is considered to be suitable for clinical use because its application in animals was feasible and safe with minimal invasiveness.
Nakajima
Hiroyuki
H
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Sakakibara
Yutaka
Y
Tambara
Keiichi
K
Iwakura
Atsushi
A
Doi
Kazuhiko
K
Marui
Akira
A
Ueyama
Koji
K
Ikeda
Tadashi
T
Tabata
Yasuhiko
Y
Komeda
Masashi
M
D000792:Angiography; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005121:Extremities; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006335:Heart Injuries / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D012680:Sensitivity and Specificity; D018608:Ultrasonography, Doppler
D003692:Delayed-Action Preparations; D016222:Fibroblast Growth Factor 2