Abstract |
Autologous cell implantation and angiogenic gene therapy have been evaluated in critical limb ischemic patients. Here, we compared the features of these strategies individually and in combination. C57BL/6J mice with ischemic hindlimbs were injected with adherent mononuclear cells (aMNCs) from bone marrow or adenovirus encoding the hepatocyte growth factor (HGF) gene (Ad-HGF). Under comparable angiogenic conditions, 10 x 10(5) aMNCs produced significantly higher amounts of VEGF and FGF-2 and stimulated the number of arterioles in ischemic muscle compared with 1 x 10(8) plaque-forming units (pfu) of Ad-HGF. Ad-HGF produced 10 times more HGF in ischemic muscle compared with aMNCs. Injection of 0.3 x 10(5) aMNCs previously transfected with Ad-HGF (aMNC/Ad-HGF) increased blood flow and elevated the numbers of capillaries and arterioles to levels comparable with that seen with 10 x 10(5) aMNCs or 1 x 10(8) pfu of Ad-HGF. Hypoxic conditions induced the apoptotic death of aMNCs. However, coincubation with HGF or aMNC/Ad-HGF protected cells against apoptosis. HGF stimulated the migration of aMNCs, and the migration capacity of the aMNC/Ad-HGF group was significantly higher than that in the aMNC/Ad-LacZ group. In conclusion, cell-based HGF gene therapy decreased the number of cells required for neovascularization. This strategy can be an effective angiogenic therapy.
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Authors | Yasutaka Yamamoto, Takashi Matsuura, Genta Narazaki, Miyoko Sugitani, Kohei Tanaka, Akihiro Maeda, Goshi Shiota, Kenzo Sato, Akio Yoshida, Ichiro Hisatome |
Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 297
Issue 4
Pg. H1329-36
(Oct 2009)
ISSN: 1522-1539 [Electronic] United States |
PMID | 19666845
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, mouse
- Fibroblast Growth Factor 2
- Hepatocyte Growth Factor
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Topics |
- Adenoviridae
(genetics)
- Animals
- Apoptosis
- Bone Marrow Transplantation
- Cell Hypoxia
- Cell Movement
- Cells, Cultured
- Combined Modality Therapy
- Disease Models, Animal
- Fibroblast Growth Factor 2
(metabolism)
- Genetic Therapy
(methods)
- Genetic Vectors
- Hepatocyte Growth Factor
(biosynthesis, genetics)
- Hindlimb
- Ischemia
(genetics, metabolism, physiopathology, therapy)
- Leukocytes, Mononuclear
(metabolism, pathology, transplantation)
- Male
- Mice
- Mice, Inbred C57BL
- Muscle, Skeletal
(blood supply)
- Neovascularization, Physiologic
- Recovery of Function
- Regional Blood Flow
- Time Factors
- Transfection
- Transplantation, Autologous
- Vascular Endothelial Growth Factor A
(metabolism)
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