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Beneficial effects of VEGF secreted from stromal cells in supporting endothelial cell functions: therapeutic
Gilda Cobellis1, Ciro Maione, Chiara Botti
1Dipartimento di Patologia Generale, Cattedra di Patologia Clinica, Seconda Università degli Studi di Napoli, Napoli, Italy. g.cobellis@unina2.it
Insights
Bone marrow cell therapy offers limb salvage for critical limb ischemia (CLI) patients. Stem cells from CLI patients showed reduced function but promoted healing via VEGF-A, indicating paracrine mechanisms drive angiogenesis.
Area of Science:
- Regenerative Medicine
- Vascular Biology
- Cell Therapy
Background:
- Critical limb ischemia (CLI) is the advanced stage of peripheral vascular disease (PVD).
- CLI patients face high risks of leg amputation, morbidity, and mortality.
- Bone marrow cell transplantation shows promise for limb salvage in no-option CLI patients.
Purpose of the Study:
- To investigate the clinical benefit of stem cell therapy in CLI patients.
- To characterize marrow-derived stromal cells from CLI patients.
- To correlate in vitro cell features with 12-month clinical outcomes.
Main Methods:
- Characterization of marrow-derived stromal cells from CLI patients.
- Assessment of cell proliferation, adhesion, and migration in vitro.
- Measurement of endothelial cell proliferation and migration stimulated by CLI-derived cells.
- Analysis of VEGF-A release from these cells.
Main Results:
- Marrow-derived stromal cells from CLI patients exhibited reduced proliferation, adhesion, and migration.
- These cells stimulated endothelial cell proliferation and migration.
- VEGF-A release was identified as a key factor in this stimulation.
- Paracrine mechanisms appear to underpin long-term angiogenesis in CLI patients treated with stem cells.
Conclusions:
- Stem cell therapy, particularly repeated autologous bone marrow cell transplantation, is effective for CLI.
- CLI patient-derived stem cells have impaired intrinsic functions but retain paracrine capabilities.
- VEGF-A mediated paracrine signaling is crucial for stem cell-driven angiogenesis and limb salvage in CLI.
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.
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