Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia

Autor: Danielle Baetens, Patrick Aebischer, Navid Alizadeh, Denys Montandon, Michael S. Pepper, Chris Rinsch, Pierre Dominique Quinodoz, Brigitte Pittet
Rok vydání: 2001
Předmět:
Vascular Endothelial Growth Factor A
Pathology
Cell Transplantation
Angiogenesis
Basic fibroblast growth factor
Wistar
Muscle
Skeletal/cytology/transplantation
Fibroblast Growth Factor 2/genetics/metabolism
Endothelial Growth Factors
Surgical Flaps
Mice
chemistry.chemical_compound
Ischemia
Surgical Flaps/blood supply
Surgical Flaps/ blood supply
Ischemia/pathology/ therapy
Genetic Therapy/methods
Lymphokines/genetics/metabolism
Lymphokines
Mice
Inbred C3H
ddc:617
Neovascularization
Pathologic
Vascular Endothelial Growth Factors
Graft Survival
Genetic transfer
Fibroblast Growth Factor 2/ genetics/metabolism
Skin Transplantation
Inbred C3H
Neovascularization
Pathologic/therapy
Vascular endothelial growth factor
Vascular endothelial growth factor A
medicine.anatomical_structure
Acute Disease
Muscle
Molecular Medicine
Gene Therapy/ methods
Female
Fibroblast Growth Factor 2
Ischemia/pathology/therapy
Blood vessel
medicine.medical_specialty
Transfection
Cell Line
Pathologic/therapy
Skeletal/cytology/transplantation
Genetics
medicine
Animals
Humans
Rats
Wistar
ddc:612
Muscle
Skeletal
Molecular Biology
Neovascularization
business.industry
Genetic Therapy
medicine.disease
Rats
Transplantation
chemistry
Cancer research
Endothelial Growth Factors/genetics/metabolism
Cattle
business
Zdroj: Gene Therapy, Vol. 8, No 7 (2001) pp. 523-33
ISSN: 1476-5462
0969-7128
DOI: 10.1038/sj.gt.3301436
Popis: Stimulating angiogenesis by gene transfer approaches offers the hope of treating tissue ischemia which is untreatable by currently practiced techniques of vessel grafting and bypass surgery. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) are potent angiogenic molecules, making them ideal candidates for novel gene transfer protocols designed to promote new blood vessel growth. In this study, an ex vivo gene therapy approach utilizing cell encapsulation was employed to deliver VEGF and FGF-2 in a continuous and localized manner. C(2)C(12) myoblasts were genetically engineered to secrete VEGF(121), VEGF(165) and FGF-2. These cell lines were encapsulated in hollow microporous polymer membranes for transplantation in vivo. Therapeutic efficacy was evaluated in a model of acute skin flap ischemia. Capsules were positioned under the distal, ischemic region of the flap. Control flaps showed 50% necrosis at 1 week. Capsules releasing either form of VEGF had no effect on flap survival, but induced a modest increase in distal vascular supply. Delivery of FGF-2 significantly improved flap survival, reducing necrosis to 34.2% (P < 0.001). Flap vascularization was significantly increased by FGF-2 (P < 0.01), with numerous vessels, many of which had a large lumen diameter, growing in the proximity of the implanted capsules. These results demonstrate that FGF-2, delivered from encapsulated cells, is more efficacious than either VEGF(121) or VEGF(165) in treating acute skin ischemia and improving skin flap survival. Furthermore, these data attest to the applicability of cell encapsulation for the delivery of angiogenic factors for the treatment and prevention of tissue ischemia.
Databáze: OpenAIRE
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