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Beneficial Effects of VEGF Secreted From Stromal Cells in Supporting Endothelial Cell Functions: Therapeutic Implications for Critical Limb Ischemia

Authors: Cobellis, Gilda; Maione, Ciro; Botti, Chiara; Coppola, Antonietta; Silvestroni, Andrea; Lillo, Stefano; Schiavone, Vincenzo; Molinari, Anna Maria; Sica, Vincenzo

Source: Cell Transplantation, Volume 19, Number 11, November 2010 , pp. 1425-1437(13)

Publisher: Cognizant Communication Corporation

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Abstract:

Critical limb ischemia (CLI) is the end stage of peripheral vascular disease (PVD). One third of CLI patients progresses to leg amputation with high associated morbidity and mortality. In no-option patients with end-stage critical limb ischemia, bone marrow cell transplantation has shown promising results, improving leg perfusion to the level of reducing major amputations and allowing limb salvage. We recently reported the successful application of an innovative protocol based on repeated autologous bone marrow cell transplantation, which resulted in an effective and feasible strategy for achieving long-term revascularization in patients with severe CLI. In an effort to understand the clinical benefit provided by stem cells therapy in patients with CLI, we characterized the marrow-derived stromal cells of CLI patients and we provided a correlation between the in vitro features of these cells and the clinical follow up at 12 months. We showed that cells derived from CLI patients had a reduced capacity to proliferate, adhere, and migrate, but that they stimulated proliferation and migration of endothelial cells through the release of VEGF-A, supporting the idea that the paracrine mechanisms underpinned the biological effects of long-term angiogenesis in CLI patients.

Keywords: Critical limb ischemia (CLI); Marrow-derived stromal cells; Trophic factors; Vascular endothelial growth factor (VEGF)

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368910X509068

Affiliations: Dipartimento di Patologia Generale, Cattedra di Patologia Clinica, Seconda Università degli Studi di Napoli, Napoli, Italy

Publication date: November 1, 2010

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

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