scholarly journals Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor in Combination with a Collagen Matrix in Chronic Hindlimb Ischemia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jianyin Zhou ◽  
Yilin Zhao ◽  
Jinling Wang ◽  
Sheng Zhang ◽  
Zhengjin Liu ◽  
...  

Although therapeutic angiogenesis by angiogenic cytokines is a feasible strategy to improve regional blood flow in ischemic regions, the optimal delivery mode needs to be established. Here we designed a complex of collagen matrix (CM) and basic fibroblast growth factor (bFGF) and evaluated its proangiogenic effect in ischemic hindlimbs. The bFGF-CM was prepared using lyophilization. The morphology, porosity and toxicity of CM were examined. The bFGF releasing profile and bioactivity of released bFGF were assessed. bFGF-CM was intramuscularly implanted into the rabbit ischemic hindlimb model. Oxygen saturation parameters (OSP) of ischemic hindlimbs was measured to evaluate the extremity perfusion at intervals. Histological examination was performed to evaluate the level of angiogenesis. The CM and bFGF-CM were of identical multiporous structure lacking cytotoxicity. The releasing profile lasted 10 days and the released bFGF remained bioactive. OSP in bFGF-CM group was significantly higher than that in CM, bFGF and ischemic groups at 2 and 4 weeks. The number of capillaries and mature vessels in bFGF-CM group were significantly greater than that in untreated control, CM and bFGF groups. Therefore, bFGF-CM enables the safe and effective long-term release of bFGF with improved angiogenesis in ischemic hindlimbs compared with CM devoid of bFGF.

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 954-960 ◽  
Author(s):  
EL Wilson ◽  
DB Rifkin ◽  
F Kelly ◽  
MJ Hannocks ◽  
JL Gabrilove

Abstract We previously showed that basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow (BM) stromal cells and significantly delays their senescence. In the present study, we demonstrated that low concentrations of bFGF (0.2 to 2 ng/mL) enhance myelopoiesis in long-term human BM culture. Addition of bFGF to long- term BM cultures resulted in an increase in (a) the number of nonadherent cells (sixfold), particularly those of the neutrophil granulocyte series; (b) the number of nonadherent granulocyte colony- stimulating factor (G-CSF)- and granulocyte-macrophage colony- stimulating factor (GM-CSF)-responsive progenitor cells; (c) the number of adherent foci of hematopoietic cells (10-fold); and (d) the number of progenitor cells in the adherent stromal cell layer. These effects were not noted with higher concentrations of bFGF (20 ng/mL). Thus, low concentrations of bFGF effectively augment myelopoiesis in human long- term BM cultures, and bFGF may therefore be a regulator of the hematopoietic system in vitro and in vivo.


2008 ◽  
Vol 1132 ◽  
Author(s):  
Jin Zhang ◽  
Richard B. Gardiner ◽  
Abdul Mumin ◽  
Richard Harris

ABSTRACTBasic fibroblast growth factor (bFGF), a protein, plays a key role in wound healing and blood vessel regeneration. However, most negative effects in vivo, or in vitro result from the over dosage of bFGF. Furthermore, it needs to keep the bFGF from protein denaturant. Thus, this study aims to develop a new delivery system based on silica nanoparticles (SiO2 NPs) dispersed in collagen patch for delivery of the bFGF in a local and prolonged manner. In this research, SiO2 NPs are used to encapsulate bFGF through a modified water-in-oil micro-emulsion. The bFGF-loaded nanoparticles afterwards are dispersed in the collagen-based matrix through a EDC cross-linking step. The in vitro release kinetics of SiO2 NPs - encapsulated bFGF with and without collagen matrix have been monitored through ELISA. In addition, the cytotoxicity of SiO2 NPs is investigated by studying the viability of Human Umbilical Vein Endothelial Cells (HUVEC) under the different concentrations of SiO2 NPs. It has found the average diameter (d) for SiO2 NPs encapsulating bFGF is 45 ± 8 nm with a loading efficiency of 72.5±3%. The maximum concentration of bFGF locally released from SiO2 NPs impregnated collagen matrix can be monitored after 30 days, while bFGF released from SiO2 NPs can be detected in 20 days. The further prolonged releasing after the nanoparticle-encapsulated bFGF laden collagen matrix is possibly due to the interaction between the nanoparticles and collagen matrix. In addition, the biocompatibility of the SiO2 NP has been investigated. We found that SiO2 NPs at the concentration of 50 μg/ml can still keep the cell alive. The results indicate that the nanoparticle-laden collagen matrix can locally deliver growth factor in a prolonged manner. This new delivery system may benefit to blood vessel regeneration and potentiate greater angiogenesis.


2010 ◽  
Vol 16 (6) ◽  
pp. 2113-2119 ◽  
Author(s):  
Hee Seok Yang ◽  
Suk Ho Bhang ◽  
Jin Wook Hwang ◽  
Dong-Ik Kim ◽  
Byung-Soo Kim

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