Cimmino, Ilaria (2022) Identification of predictive biomarkers for cell-based therapy in critical limb ischemia. [Tesi di dottorato]

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Item Type:	Tesi di dottorato
Resource language:	English
Title:	Identification of predictive biomarkers for cell-based therapy in critical limb ischemia
Creators:	Creators Email Cimmino, Ilaria ilariacimmino@hotmail.it
Date:	10 March 2022
Number of Pages:	62
Institution:	Università degli Studi di Napoli Federico II
Department:	Scienze Mediche Traslazionali
Dottorato:	Medicina clinica e sperimentale
Ciclo di dottorato:	34
Coordinatore del Corso di dottorato:	nome email Beguinot, Francesco beguino@unina.it
Tutor:	nome email Oriente, Francesco UNSPECIFIED
Date:	10 March 2022
Number of Pages:	62
Keywords:	Biomarkers, cell-based therapy, critical limb ischemia
Settori scientifico-disciplinari del MIUR:	Area 06 - Scienze mediche > MED/05 - Patologia clinica
Date Deposited:	21 Mar 2022 10:04
Last Modified:	28 Feb 2024 10:51
URI:	http://www.fedoa.unina.it/id/eprint/14432

Collection description

Critical limb ischemia (CLI) is a pathological condition characterized by chronic ischemic at-rest pain, intermittent claudication, ulcers, or gangrene in one or both legs related to peripheral artery disease. Smokers, people affected by atherosclerosis, diabetes mellitus, hypertension and hyperhomocysteinemia have a high risk for CLI and prevalence of CLI is continuously rising in most countries as consequence of the several risk factors. Patients with CLI may develop irreversible ischemic damage to the leg or foot if they do not receive appropriate treatment and this may lead to the need for amputation. Actually, the main goal of critical limb ischemia treatment is to preserve the limb by reestablishing blood flow to the affected area. After surgical and/or endovascular treatment, approximately 50-60% of patients benefit, while the remaining will undergo primary amputation or conservative medical therapy. Biologic therapies, which include gene therapy and cellular therapy, offer the potential to promote wound healing and prevent amputation in patients who otherwise have poor options for revascularization. In this study, I focused my attention on the application of bone marrow cellular and soluble components in order to identify prognostic biomarkers in patients undergoing stem cells therapy. To this aim, 40 patients were enrolled in the study. For each patient, bone marrow (BM) samples were collected before and after cell concentration with Sepax-2 instrument. In parallel, peripheral blood (PB) samples were collected at baseline (T0). BM samples showed a statistically significant increase of EPC fraction compared to PB samples. Among nucleate cells from BM concentrate EPCs and MSCs were isolated in presence of specific cell-culture conditions. Pro-angiogenic cytokines and chemokines were found at higher concentrations in BM compared to PB. Among the released factors, IL-9 and PDGF concentration, both in serum and in BM, positively correlated with improvement (T1-T0) of treadmill test (ΔTT) and transcutaneous partial pressure of oxygen (ΔtcpO2), respectively. Thus, this study confirmed the useful application of cell therapy in improving pain and revascularization in patients affected by CLI and promoted soluble factors, such as IL-9 and/or PDGF, as prognostic factors in the management of the pathology.

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