title: Combined therapy with sonic hedgehog gene transfer and bone marrow-derived endothelial progenitor cells enhances angiogenesis and myogenesis in the ischemic skeletal muscle.
abstract: We have previously demonstrated that sonic hedgehog (Shh) gene transfer improves angiogenesis in the setting of ischemia by upregulating the expression of multiple growth factors and enhancing the incorporation of endogenous bone marrow (BM)-derived endothelial progenitor cells (EPCs). In this study, we hypothesized that combined therapy with Shh gene transfer and BM-derived EPCs is more effective than Shh gene therapy alone in an experimental model of peripheral limb ischemia. We used old mice, which have a significantly reduced angiogenic response to ischemia, and compared the ability of Shh gene transfer, exogenous EPCs, or both to improve regeneration after ischemia. We found a significantly higher capillary density in the Shh + EPC-treated muscles compared to the other experimental groups. We also found that Shh gene transfer increases the incorporation and survival of transplanted EPCs. Finally, we found a significantly higher number of regenerating myofibers in the ischemic muscles of mice receiving combined treatment with Shh and BM-derived EPCs. In summary, the combination of Shh gene transfer and BM-derived EPCs more effectively promotes angiogenesis and muscle regeneration than each treatment individually and merits further investigation for its potential beneficial effects in ischemic diseases.
authors: Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
authors: Mariangela
authors: M
authors: Palladino
authors: Ilaria
authors: I
authors: Gatto
authors: Valentina
authors: V
authors: Neri
authors: Egidio
authors: E
authors: Stigliano
authors: Roy C
authors: RC
authors: Smith
authors: Enrico
authors: E
authors: Pola
authors: Stefania
authors: S
authors: Straino
authors: Eleonora
authors: E
authors: Gaetani
authors: Maurizio
authors: M
authors: Capogrossi
authors: Giuseppe
authors: G
authors: Leone
authors: Lynn
authors: L
authors: Hlatky
authors: Roberto
authors: R
authors: Pola
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D042783:Endothelial Cells / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D053823:Hedgehog Proteins / Q000235:genetics*; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D012038:Regeneration
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human