Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: a controlled randomized phase 1/2 clinical trial.

Autor: Arango-Rodríguez ML; Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL Internacional, Floridablanca, Colombia. Electronic address: martha.arango@foscal.com.co., Solarte-David VA; Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia; Facultad de Ingeniería, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia 680003., Becerra-Bayona SM; Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia., Callegari E; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA., Paez MD; Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA., Sossa CL; Fundación Oftalmológica de Santander Carlos Ardila Lulle Floridablanca, Colombia; Programa para el Tratamiento y Estudio de Enfermedades Hematológicas y Oncológicas de Santander (PROTEHOS), 681004153 Floridablanca, Colombia., Vera MEO; Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia., Mateus LC; Fundación Oftalmológica de Santander Carlos Ardila Lulle Floridablanca, Colombia., Eduardo Serrano S; Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia., Ardila-Roa AK; Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL Internacional, Floridablanca, Colombia., Viviescas LTG; Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL Internacional, Floridablanca, Colombia.
Jazyk: angličtina
Zdroj: Cytotherapy [Cytotherapy] 2022 Oct; Vol. 24 (10), pp. 1035-1048. Date of Electronic Publication: 2022 Jul 02.
DOI: 10.1016/j.jcyt.2022.04.002
Abstrakt: Background: Diabetes-related foot complications have been identified as the most common isolated cause of morbidity among patients with diabetes and the leading cause of amputation. Therefore, new strategies to stimulate skin regeneration may provide a novel therapeutic approach to reduce non-healing ulcer disease. Recently, we demonstrated in proof-of-concept in humans that administration of allogeneic bone marrow mesenchymal stromal cellss derivatives (allo-hBM-MSCDs) is effective in a similar way to the use of allogeneic bone marrow mesenchymal stromal cellss (allo-hBM-MSCs) in grade 2 diabetic foot ulcers (DFUs).
Aim: To assess the safety and efficacy profile of the allo-hBM-MSCDs relative to the conventional approach (PolyMen® dressing) in 1/2 clinical trial phases in patients with grade 1 and 2 DFUs.
Methods: In the present study, we used 2 doses of allo-hBM-MSCDs (1 mL) or 1 dose of allo-hBM-MSCs (1 × 106 cells) intradermally injected around wounds and assessed their safety and effectiveness, relative to the conventional approach (PolyMem dressing). Allo-hBM-MSCDs and allo-hBM-MSCs were produced in a certified Good Manufacturing Practice-type Laboratory. Patients with grade 1 and 2 DFUs were randomized to receive allo-hBM-MSCDs (n=12), allo-hBM-MSCs (n=6) or conventional treatment (PolyMem dressing) (n=10). The wound-healing process was macroscopically evaluated until the complete closure of the ulcers.
Results: No adverse events were reported. Patients with grade 1 and 2 DFUs treated with either allo-hBM-MSCDs or allo-hBM-MSCs, achieved greater percentages of wound closure, enhanced skin regeneration in shorter times and a greater ulcer-free survival relative to the patients who received conventional treatment. Finally, through proteomic analysis, we elucidated the proteins and growth factors that are secreted by allo-hBM-MSCs and relevant to the wound-healing process. In addition, by combining proteomics with Gene Ontology analysis, we comprehensively classified secreted proteins on both biological process and molecular function.
Conclusions: In this phase 1/2 trial, our cumulative results suggest that 2 doses of allo-hBM-MSCDs combined with a wound dressing are a safe and effective treatment for grade 1 and 2 DFUs.
Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article.
(Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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