Dataset Information

Long-term changes following pre-conditioned circulating angiogenic cells therapy in critical limb ischemia

ABSTRACT: Critical limb ischemia (CLI), results from a severe blockade of the arterial vessels, is usually correlated to atherosclerosis. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative potential, although the mechanisms of action of these cells as well as their response to pathological conditions remains unclear. Previously, we have shown that the incubation ex vivo of CACs with factors secreted by atheroma plaques promotes the activation and mobilization of these cells. Herein, we have evaluated the long-term effect of CACs administration in CLI mice, whether pre-stimulated or not with atherosclerotic factors.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Adult Endothelial Progenitor Cell, Femoral Muscle

DISEASE(S): Limb Ischemia

SUBMITTER: Lucía Beltrán-Camacho

LAB HEAD: Mª Carmen Duran-Ruiz

PROVIDER: PXD024132 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

Long Term Response to Circulating Angiogenic Cells, Unstimulated or Atherosclerotic Pre-Conditioned, in Critical Limb Ischemic Mice.

Beltrán-Camacho Lucía L Jiménez-Palomares Margarita M Sanchez-Gomar Ismael I Rosal-Vela Antonio A Rojas-Torres Marta M Eslava-Alcon Sara S Alonso-Piñero Jose Angel JA González-Rovira Almudena A Extremera-García Mª Jesús MJ Conejero Rosario R Doiz Esther E Rodriguez-Piñero Manuel M Larsen Martin R MR Duran-Ruiz Mª Carmen MC

Biomedicines 20210903 9

Critical limb ischemia (CLI), the most severe form of peripheral artery disease, results from the blockade of peripheral vessels, usually correlated to atherosclerosis. Currently, endovascular and surgical revascularization strategies cannot be applied to all patients due to related comorbidities, and even so, most patients require re-intervention or amputation within a year. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative ...[more]

PMID: 34572333

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Project description:Critical limb threatening ischemia (CLTI), the most severe manifestation of peripheral artery disease, results from the chronic blockade of peripheral vessels, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization and reversal of CLTI. However, the variety in cell types and cell combinations, administration routes or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal “cellular-cocktail” for these patients, prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated and compared, for the first time, the regenerative and vasculogenic potential of endothelial colony forming cells (ECFCs) isolated from either adipose-tissue (AT-ECFCs) or umbilical cord blood (CB-ECFCs), in combination with AT-derived MSCs, in a murine model of CLTI. Furthermore, the long-term molecular changes in CLTI and in response to both combinations have been analyzed in a proteomic quantitative approach. Overall, the administration of AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia, which appeared associated to an increased number of vessels in AT treated mice or with wider vessels in CB. Besides, they both modulated the inflammatory and necrotic processes, although the CB group presented the slowest ischemic progression along the assay. Furthermore, many of the protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs induced revascularization (immune response, vascular repair, muscle regeneration, etc).

			Action	DRS
	Lucia_LFQ.msf	Msf
	MRL_Lucia_01.raw	Raw
	MRL_Lucia_010.raw	Raw
	MRL_Lucia_011.raw	Raw
	MRL_Lucia_012.raw	Raw