Recently, I have started my teaching career as an associate lecturer (2022) in the University of Leon within the area of pathological anatomy, participating in courses and teaching innovation projects. Additionally, I have contributed to the development and training of young researchers within the department, I have contributed to the creation of the spin off Dental Biomedical associated with the University of León, I have carried out several complementary training courses, training of specialized techniques and I have participated in the organization of R&D activities.
EDUCATION
I started my research career during the completion of the Master's project (2016) in the Biological Drug Applications Group, focused on the study of exosomes derived from mesenchymal stem cells (ad-MSCs). My PhD thesis (2017-2021) was focused on the application of ad-MSCs in discogenic pain and neuropathic pain, funded within the framework of various research contracts. The research conducted generated three first author scientific publications in international journals, five contributions to national and international congresses, a collaborative stay with the CIC bioGUNE center of excellence and the participation of twol conferences.
RESEARCH, TEACHING, or OTHER INTERESTS
Cell Biology, Biotechnology, Molecular Biology, Molecular Medicine
The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study Elsa González-Cubero, Maria Luisa González-Fernández, Marta Esteban-Blanco, Saúl Pérez-Castrillo, Esther Pérez-Fernández, et al. International Journal of Molecular Sciences, 2024 Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF-κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9. These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms.
Equine Corneal Wound Healing Using Mesenchymal Stem Cell Secretome: Case Report Alejandro Casado-Santos, Elsa González-Cubero, Maria Luisa González-Fernández, Yaiza González-Rodríguez, Mª Belén García-Rodríguez, et al. Animals, 2024 Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of the ASC secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.
Regenerative Medicine Applied to Musculoskeletal Diseases in Equines: A Systematic Review Andrea Pérez Fraile, Elsa González-Cubero, Susana Martínez-Flórez, Elías R. Olivera, Vega Villar-Suárez Veterinary Sciences, 2023 Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies categorized by the therapeutic approach used: platelet-rich plasma, conditioned autologous serum, mesenchymal stem cells, and secretome. These therapies reduce healing time, promote regeneration of fibrocartilaginous tissue, improve cellular organization, and improve joint functionality and sustainability. In conclusion, regenerative therapies using platelet-rich plasma, conditioned autologous serum, equine mesenchymal stem cells, and the emerging field of the secretome represent a promising and highly effective approach for the treatment of joint pathologies in horses, implying a valuable advance in equine healthcare.
Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage Elsa González-Cubero, María Luisa González-Fernández, María Rodríguez-Díaz, Marta Palomo-Irigoyen, Ashwin Woodhoo, et al. Frontiers in Cellular Neuroscience, 2022 BackgroundNeuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM).MethodsTo this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy.ResultsOur data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins.ConclusionFindings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology.
Isolation and characterization of exosomes from adipose tissue-derived mesenchymal stem cells Elsa González‐Cubero, María Luisa González‐Fernández, Laura Gutiérrez‐Velasco, Eliezer Navarro‐Ramírez, Vega Villar‐Suárez Journal of Anatomy, 2021 Mesenchymal stem cells (MSCs) are the subject of intense research as they are a potential therapeutic tool for several clinical applications. The new MSCs action models are focused on the use of MSC‐derived secretome which contains several growth factors, cytokines, microRNAs, and extracellular vesicles such as exosomes. Exosomes have recently emerged as a component with great potential involved as mediators in cellular communication. The isolation and identification of exosomes has made it possible for them to be used in cell‐free therapies. The purposes of this study are: (i) to detect exosomes released into adipose‐derived MSC conditioned cell culture medium, (ii) to identify exosome morphology, and (iii) to carry out a complete characterization of said exosomes. Moreover, it is aimed at determining which method for exosome isolation would be best to use. Precipitation has been identified as a highly useful method of exosome isolation since it provides higher efficiency and purity values than other methods. A broad characterization of the exosomes present in the MSC‐conditioned medium was also carried out. This work fills a gap in the existing literature on bioactive molecules which have attracted a great deal of interest due to their potential use in cellular therapies.
Effect of mesenchymal stem cells combined with chondroitin sulfate in an in vitro model of osteoarthritis American Journal of Translational Research, 2021
