Safety and Efficacy of Therapeutic Angiogenesis as a Novel Treatment in Patients with Critical Limb Ischemia

Lara-Hernández, R.; Lozano-Vilardell, P.; Blanes, P.; Torreguitart-Mirada, N.; Galmés, Antonio; Besalduch, Joan

doi:10.1016/j.avsg.2009.10.012

Cited by 108 publications

(63 citation statements)

References 37 publications

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“…Nevertheless, cell therapy for limb ischemia using EPCs imply autologous transplantation of cells because of the expression of HLA antigens, and EPCs obtained from peripheral blood require ex vivo expansion. The need of both autologous cells and in vitro expansion of the EPCs isolated from peripheral blood limit this procedure because the amount of cells required for transplantation is achieved only after several days of culture (6,7). Our findings demonstrate the ability of EPC-derived MVs to induce a neoangiogenic program after ischemia.…”

Section: Discussionmentioning

confidence: 99%

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Endothelial Progenitor Cell-Derived Microvesicles Improve Neovascularization in a Murine Model of Hindlimb Ischemia

Ranghino

Cantaluppi

Grange

et al. 2012

Int J Immunopathol Pharmacol

146

129

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Paracrine mediators released from endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis following ischemia. Recently, we demonstrated that microvesicles (MVs) derived from EPCs are able to activate an angiogenic program in quiescent endothelial cells by a horizontal transfer of RNA. In this study we aim to investigate whether EPC-derived MVs are able to induce neoangiogenesis and to enhance recovery in a murine model of hindlimb ischemia. Hindlimb ischemia was induced in severe combined immunodeficient (SCID) mice by ligation and resection of the left femoral artery and mice were treated with EPC-derived MVs (MVs), RNase-inactivated MVs (RnaseMVs), fibroblastderived MVs or vehicle alone as control (CTL). Since MVs contained the angiogenic miR-126 and miR-296, we evaluated whether microRNAs may account for the angiogenic activities by treating mice with MVs obtained from DICER-knock-down EPC (DICER-MVs). Peripheral arterial disease, caused by atherosclerotic occlusion of the leg arteries, is an important manifestation of systemic atherosclerosis along with coronary heart disease and cerebrovascular disease. The age-adjusted prevalence of peripheral arterial disease is approximately 12%, and affects men and women equally. The typical clinical manifestation is claudication, nevertheless 5% ofpatients undergo an amputation within 5 years (1,2).

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Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that stem cells and progenitor cells such as endothelial progenitor cells (EPCs) contribute to neoangiogenesis during hindlimb ischemia (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Endothelial Progenitor Cell-Derived Microvesicles Improve Neovascularization in a Murine Model of Hindlimb Ischemia

Ranghino

Cantaluppi

Grange

et al. 2012

Int J Immunopathol Pharmacol

146

129

View full text Add to dashboard Cite

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“…Cells were labeled with the R-phycoenythrin (PE)-conjugated monoclonal CD133 antibody (Miltenyi Biotech, Gladbach, Germany) or/and fluorescein Isothiocyanate (FITC)-conjugated CD34 monoclonal antibody (BD Pharmingen, San Jose, CA) for 20 min at room temperature. Cells stained positive for CD34 and CD133 (Santa Cruz Biotech, Santa Cruz, CA) were selected as EPCs (Friedrich et al, 2006;Lam et al, 2008;Lara-Hernandez et al, 2010).…”

Section: Epcs Isolation and Analysismentioning

confidence: 99%

Progesterone Increases Circulating Endothelial Progenitor Cells and Induces Neural Regeneration after Traumatic Brain Injury in Aged Rats

Wang

Kan

et al. 2012

Journal of Neurotrauma

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Vascular remodeling plays a key role in neural regeneration in the injured brain. Circulating endothelial progenitor cells (EPCs) are a mediator of the vascular remodeling process. Previous studies have found that progesterone treatment of traumatic brain injury (TBI) decreases cerebral edema and cellular apoptosis and inhibits inflammation, which in concert promote neuroprotective effects in young adult rats. However, whether progesterone treatment regulates circulating EPC level and fosters vascular remodeling after TBI have not been investigated. In this study, we hypothesize that progesterone treatment following TBI increases circulating EPC levels and promotes vascular remodeling in the injured brain in aged rats. Male Wistar 20-month-old rats were subjected to a moderate unilateral parietal cortical contusion injury and were treated with or without progesterone (n = 54/group). Progesterone was administered intraperitoneally at a dose of 16mg/kg at 1 h post-TBI and was subsequently injected subcutaneously daily for 14 days. Neurological functional tests and immnunostaining were performed. Circulating EPCs were measured by flow cytometry. Progesterone treatment significantly improved neurological outcome after TBI measured by the modified neurological severity score, Morris Water Maze and the long term potentiation in the hippocampus as well as increased the circulating EPC levels compared to TBI controls ( p < 0.05). Progesterone treatment also significantly increased CD34 and CD31 positive cell number and vessel density in the injured brain compared to TBI controls ( p < 0.05). These data indicate that progesterone treatment of TBI improves multiple neurological functional outcomes, increases the circulating EPC level, and facilitates vascular remodeling in the injured brain after TBI in aged rats.

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“…Vascular regenerative therapy improves the flow of blood to ischemic tissues by inducing neovascularization in patients with vascular occlusive diseases (1)(2)(3)(4)(5)(6)(7)(8). Therapeutic methods include the direct delivery of vascular growth factors including vascular endothelial growth factor, basic fibroblast growth factor (bFGF) and hepatocyte growth factor, the delivery of genes into host cells for the on-site production of vascular growth factors and the direct delivery of somatic stem cells capable of generating new vessels (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model

Nitta

Nitta-Seko

Sonoda

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. The purpose of this study was to compare the results of delivering low doses of growth factor iteratively (20 µg x5) via a reservoir system with results obtained following a single administration of 100 µg of growth factor. The delivery systems using gelatin microspheres (GMS) facilitate the controlled release of drugs. The controlled release of growth factors at specific sites is essential for vascular regeneration. An ischemic hind-limb model was established in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter was infused in the reservoir system. The rabbits were divided into three equal groups: group 1 received 20 µg iteratively (x5) via the reservoir, a single dose of 100 µg growth factor was administered to group 2 and group 3 was the saline control. The therapeutic effects were evaluated by measuring the thigh temperature, blood pressure and blood flow. An immunohistological analysis was also performed for CD31. No significant difference was observed between preand post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood pressure and blood flow results from each group. Pathological analysis revealed that the number of regenerated vessels was significantly higher in the group treated iteratively with low-dose bFGF.

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Safety and Efficacy of Therapeutic Angiogenesis as a Novel Treatment in Patients with Critical Limb Ischemia

Cited by 108 publications

References 37 publications

Endothelial Progenitor Cell-Derived Microvesicles Improve Neovascularization in a Murine Model of Hindlimb Ischemia

Endothelial Progenitor Cell-Derived Microvesicles Improve Neovascularization in a Murine Model of Hindlimb Ischemia

Progesterone Increases Circulating Endothelial Progenitor Cells and Induces Neural Regeneration after Traumatic Brain Injury in Aged Rats

Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model

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