Person: Fernández Gutiérrez, Benjamín
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First Name
Benjamín
Last Name
Fernández Gutiérrez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina
Area
Medicina
Identifiers
3 results
Search Results
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Item RNA sequencing of mesenchymal stem cells reveals a blocking of differentiation and immunomodulatory activities under inflammatory conditions in rheumatoid arthritis patients(Arthritis Research & Therapy, 2019) Lamas, José Ramón; Fernández Gutiérrez, Benjamín; Mucientes, Arkaitz; Marco Martínez, Fernando; Lópiz Morales, María Yaiza; Jover Jover, Juan Ángel; Abasolo, Lydia; Rodríguez Rodríguez, LuisIntroduction: Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act as regulators of inflammation. Thus, in addition to their regenerating potential, their interest has been extended to their possible use in cell therapy strategies for treatment of immune disorders. Objective: To analyze, by RNA-seq analysis, the transcriptome profiling of allogenic MSCs under RA lymphocyte activation. Methods: We identified the differentially expressed genes in bone marrow mesenchymal stem cells after exposure to an inflammatory environment. The transcriptome profiling was evaluated by means of the precise measurement of transcripts provided by the RNA-Seq technology. Results: Our results evidenced the existence of blocking of both regenerative (differentiation) and immunomodulatory phenotypes under inflammatory conditions characterized by an upregulation of genes involved in immune processes and a simultaneous downregulation of genes mainly involved in regenerative or cell differentiation functions. Conclusions: We conclude that the two main functions of MSCs (immunomodulation and differentiation) are blocked, at least while the inflammation is being resolved. Inflammation, at least partially mediated by gamma-interferon, drives MSCs to a cellular distress adopting a defensive state. This knowledge could be of particular interest in cases where the damage to be repaired has an important immune-mediated component.Item Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full thickness rotator cuff tears(Trials, 2019) Lamas, José Ramón; García Fernández, Carlos; Tornero Esteban, Pilar; Lópiz Morales, María Yaiza; Rodríguez Rodríguez, Luis; Ortega Medina, Luis; Fernández Gutiérrez, Benjamín; Marco Martínez, FernandoPurpose: The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon. Methods: This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007-007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS). Constant score has four domains including pain (15 possible points), activities of daily living (20 possible points), mobility (40 possible points), and strength (25 possible points). Scores range from 0 points (most disability) to 100 points (least disability). The structural integrity of the repaired tendon was assessed by magnetic resonance imaging (MRI) according to Patte and Thomazeau classification criteria. The primary study end point was an improvement in the Constant score by 20 points at one year compared to initial assessment. Results: The trial was stopped due to adverse effects observed in both groups. Only thirteen patients were included and analyzed. The Constant questionnaire showed a significant improvement in the MSC treatment group compared with the preoperative data (p = 0.0073). Secondary outcome measures were similar in both groups. Conclusions: Our study showed preliminary inconclusive clinical outcomes in the patients treated with MSCs. Adverse events revealed the need for further approaches using scaffolds of a different nature or perhaps no scaffolds, in the context of small joints. Trial registration: Eudra-CT, 2007-007630-19. Registered on 30 January 2008. Level of evidence: A Level 1 of evidence treatment study.Item Check-control of inflammation displayed by bone marrow mesenchymal stem cells in rheumatoid arthritis patients(Immunotherapy, 2019) Lamas, José Ramón; Mucientes, Arkaitz; Lajas Petisco, Cristina De Jesús; Fernández Gutiérrez, Benjamín; Lópiz Morales, María Yaiza; Marco Martínez, Fernando; Jover Jover, Juan Ángel; Abasolo, Lydia; Rodríguez Rodríguez, LuisBackground: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.