Beneficial effects of VEGF secreted from stromal cells in supporting endothelial cell functions: therapeutic implications for critical limb ischemia.
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.
Cobellis
Gilda
G
Dipartimento di Patologia Generale, Cattedra di Patologia Clinica, Seconda Università degli Studi di Napoli, Napoli, Italy. g.cobellis@unina2.it
Maione
Ciro
C
Botti
Chiara
C
Coppola
Antonietta
A
Silvestroni
Andrea
A
Lillo
Stefano
S
Schiavone
Vincenzo
V
Molinari
Anna Maria
AM
Sica
Vincenzo
V
D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005121:Extremities / Q000098:blood supply*; D020869:Gene Expression Profiling; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D017154:Stromal Cells / Q000378:metabolism*; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A