Combined therapy with sonic hedgehog gene transfer and bone marrow-derived endothelial progenitor cells enhances angiogenesis and myogenesis in the ischemic skeletal muscle

Mariangela Palladino, Ilaria Gatto, Valentina Neri, Egidio Stigliano, Roy C. Smith, Enrico Pola, Stefania Straino, Eleonora Gaetani, Maurizio Capogrossi, Giuseppe Leone, Lynn Hlatky, Roberto Pola

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)425-431
Number of pages7
JournalJournal of Vascular Research
Volume49
Issue number5
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Hedgehogs
Muscle Development
Skeletal Muscle
Bone Marrow
Genes
Ischemia
Therapeutics
Muscles
Regeneration
Endothelial Progenitor Cells
Genetic Therapy
Intercellular Signaling Peptides and Proteins
Theoretical Models
Extremities

Keywords

  • Endothelial progenitor cells
  • Peripheral ischemia
  • Sonic hedgehog gene therapy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Combined therapy with sonic hedgehog gene transfer and bone marrow-derived endothelial progenitor cells enhances angiogenesis and myogenesis in the ischemic skeletal muscle. / Palladino, Mariangela; Gatto, Ilaria; Neri, Valentina; Stigliano, Egidio; Smith, Roy C.; Pola, Enrico; Straino, Stefania; Gaetani, Eleonora; Capogrossi, Maurizio; Leone, Giuseppe; Hlatky, Lynn; Pola, Roberto.

In: Journal of Vascular Research, Vol. 49, No. 5, 08.2012, p. 425-431.

Research output: Contribution to journalArticle

Palladino, M, Gatto, I, Neri, V, Stigliano, E, Smith, RC, Pola, E, Straino, S, Gaetani, E, Capogrossi, M, Leone, G, Hlatky, L & Pola, R 2012, 'Combined therapy with sonic hedgehog gene transfer and bone marrow-derived endothelial progenitor cells enhances angiogenesis and myogenesis in the ischemic skeletal muscle', Journal of Vascular Research, vol. 49, no. 5, pp. 425-431. https://doi.org/10.1159/000337921
Palladino, Mariangela ; Gatto, Ilaria ; Neri, Valentina ; Stigliano, Egidio ; Smith, Roy C. ; Pola, Enrico ; Straino, Stefania ; Gaetani, Eleonora ; Capogrossi, Maurizio ; Leone, Giuseppe ; Hlatky, Lynn ; Pola, Roberto. / Combined therapy with sonic hedgehog gene transfer and bone marrow-derived endothelial progenitor cells enhances angiogenesis and myogenesis in the ischemic skeletal muscle. In: Journal of Vascular Research. 2012 ; Vol. 49, No. 5. pp. 425-431.
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