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Pathophysiology and Regenerative Medicine
Pathophysiology and Regenerative Medicine (PRMG)
Principal Investigator: Rafael Moreno-Luna, PhD
ORCID: 0000-0002-9840-5078
Email: rmluna@sescam.jccm.es
MISSION STATEMENT
Understanding why tissues fail to repair in order to discover how to restore them.
We investigate why some damaged tissues fail to repair properly, particularly in clinical settings where current therapeutic options remain insufficient. Our work integrates clinical expertise, biomedical research, and regenerative medicine to develop strategies aimed at promoting tissue repair in complex injuries, chronic wounds, and vascular damage.
WHO WE ARE
Led by Dr. Rafael Moreno-Luna, the Pathophysiology and Regenerative Medicine Group (PRMG) has a multidisciplinary team that brings together biomedical, clinical, and healthcare professionals. This composition makes it possible to formulate scientific questions that arise from clinical and healthcare needs and to develop strategies aimed at problems that remain unresolved in the repair of damaged tissues.
Our research focuses on understanding the pathophysiological processes that lead to tissue damage, tissue loss, or insufficient repair, with special attention to vascular damage, alterations in the tissue microenvironment, inflammation, and the functional behavior of patient-derived cells.
One of the group’s main clinical applications is the study of pressure injuries and other chronic wounds, especially in people with spinal cord injury. In addition, the group’s interests extend to other settings of tissue and vascular damage, such as ischemia, revascularization, vascular reconstruction, and tissue bioengineering.
Our objective is to understand the mechanisms that determine the repair of damaged human tissues in order to develop our own safe, reproducible, and clinically translatable cellular and molecular therapeutic strategies, oriented toward regenerative medicine and advanced therapies.
WHAT PROBLEM ARE WE TRYING TO SOLVE
The repair of damaged tissue does not depend on a single factor. For tissue to regenerate properly, it requires functional cells, a controlled inflammatory environment, appropriate molecular signals, extracellular matrix, vascular supply, and precise coordination among the different cell populations involved.
In complex injuries, such as pressure injuries and other chronic wounds, these mechanisms may become altered. The tissue loses its capacity for repair, the local microenvironment becomes unfavorable, and patient-derived cells may change their functional behavior.
For this reason, our group studies not only the final lesion, but also the mechanisms that explain why the lesion appears, why it becomes chronic, and how its repair could be promoted through regenerative medicine strategies.
OUR MAIN RESEARCH AREAS
PRMG works in five main research areas, all connected by a common goal: to understand tissue and vascular damage and move toward repair strategies and regenerative medicine.
1. Pathophysiology of Tissue Damage
We study the cellular, molecular, and tissue-level mechanisms that determine damage, tissue loss, or insufficient repair.
Our interest focuses on understanding how local damage, inflammation, vascular alteration, the tissue microenvironment, and the functional status of patient-derived cells influence the progression of complex injuries.
2. Pressure Injuries and Chronic Wounds
One of the group’s main applications is the study of pressure injuries and other chronic wounds in people with spinal cord injury.
In this context, we analyze how the pathophysiology associated with spinal cord injury, the condition of the tissue, alterations in the local microenvironment, and the functionality of patient-derived cells may influence the development, progression, and repair of these injuries.
3. Cells with Regenerative Potential
We characterize mesenchymal stem/stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) derived from human adipose tissue, evaluating their reparative, paracrine, immunomodulatory, angiogenic, vasculogenic, and tissue-interaction capacities.
ECFCs allow us to study the formation and repair of vascular networks, an essential component for tissues to receive oxygen, nutrients, and reparative signals. In addition, they act as a sensitive cellular model to analyze how certain pathological environments alter endothelial function, to understand cardiovascular pathophysiology, and to explore possible risk factors or biomarkers associated with vascular damage.
MSCs, in addition to their relationship with the vascular component, can modulate the inflammatory environment, secrete trophic factors, influence the behavior of other cells, and contribute to organizing the regenerative microenvironment.
4. Cellular Modulation and Regenerative Medicine
A relevant part of our current research focuses on studying how pharmacological modulation of mesenchymal and endothelial cells can improve their functional behavior.
This approach seeks to promote broad tissue repair processes, including regulation of the inflammatory microenvironment, secretion of reparative factors, interaction with other cells, and possible contribution to the reconstruction of compromised tissues in complex injuries.
5. Revascularization, Ischemia, and Vascular Bioengineering
One of the group’s main objectives is the development of an ECFC/MSC cellular platform derived from human adipose tissue, aimed at vascular repair and the preclinical validation of advanced cell therapies in severe vascular disease.
This line integrates the study of revascularization, tissue ischemia, and vascular bioengineering, with the aim of generating safe, reproducible, and clinically translatable cell-processing protocols.
To this end, it incorporates functional characterization processes, quality control, and adaptation to GMP standards, which are required for the clinical production of advanced therapies. This approach is aligned with the regulatory requirements applicable to advanced therapy medicinal products and is intended to facilitate evaluation by the Spanish Agency for Medicines and Medical Devices. The purpose is to advance toward therapeutic strategies capable of restoring the vascular component, improving the regenerative environment, and promoting tissue recovery.
WHO MAKES UP OUR TEAM
PRMG brings together a multidisciplinary team that integrates biomedical, clinical, and healthcare backgrounds, allowing research to be approached from a translational perspective connected to the real needs of patients.
Group Members:
- Rafael Moreno-Luna, PhD — Principal Investigator / R4 and Head of PRMG. PhD in Biomedicine. R3-certified researcher by the Spanish State Research Agency.
- Matilde Castillo Hermoso, PhD — Senior Researcher / R3 with healthcare and teaching activity. Nurse, PhD in Health Care, degree in Anthropology, and Associate Professor at the University of Castilla-La Mancha.
- Laura Silva Colmenar, PhD — Postdoctoral Researcher / R2. Degree in Biology, Master’s degree in Translational Medicine Research, and PhD in Biomedical Research.
- Mario Martínez-Torija — Predoctoral Researcher / R1 with healthcare activity. Degree in Nursing and Biochemistry. Master’s degree in Immunology Research.
- Ángela Santos De La Mata — Predoctoral Researcher / R1. Degree in Biotechnology. Master’s degree in Biomedical Engineering.
- M.ª Ángeles Ruiz de Infante — Researcher / R1. Degree in Nursing. Regional Coordination of the Occupational Risk Prevention Service, SESCAM.
- Rafael E. Peña Rodríguez — Researcher / R1 with healthcare activity. Specialist Physician in Occupational Medicine. Master’s degree in Medical Expert Assessment and Bodily Injury Evaluation.
WHO FUNDS OUR RESEARCH
PRMG’s research is supported by competitive funding and by projects aimed at developing strategies in regenerative medicine, cell therapy, tissue repair, and vascular pathophysiology.
Active Funded Projects
1. Agencia de Investigación e Innovación de Castilla-La Mancha, INNOCAM 2024 (2024-2027); Ref.: SBPLY/23/180225/000083. Combined therapy for the treatment of pressure ulcers in patients with spinal cord injury. Validation in a preclinical study. Moreno-Luna R (PI). In collaboration with the Neuroinflammation Group, Esteban Pedro F. (PI). Funding awarded: €126,000.
2. Agencia Estatal de Investigación, AEI-2023 (2023-2026) Ref.: PID2022-137080OB-I00. Differential markers from MSCs and role of the ECS in the design of combined therapies for pressure ulcer treatment in spinal cord injured patients. Moreno-Luna R (PI). In collaboration with the Neuroinflammation Group, Molina-Holgado E (PI). Funding awarded: €187,500.
3. SESCAM & Consejería Sanidad de CLM (2023-2026) Ref.: MRTA/SLB1. Combined use of endothelial stem/progenitor cells derived from adipose tissue of patients with spinal cord injury for the repair/regeneration of chronic wounds. Biosafety study. Moreno-Luna R (PI). Funding awarded: €100,980.
Completed Funded Projects
1. Instituto de Salud Carlos III, AES-2018 (2019-2023) Ref.: PI18/00427. Preclinical study: combined use of endothelial stem/progenitor cells derived from adipose tissue of patients with spinal cord injury for the repair/regeneration of pressure ulcers. Moreno-Luna R (PI).
2. The European Proteomics Infrastructure Consortium (2021-2022) Ref.: EPIC-XS-0000212. Role of resident adipose tissue-derived stem and progenitor cells in the regeneration/repair of damaged tissues from pressure ulcers in patients with spinal cord injury. Moreno-Luna R (PI). In collaboration with the Department of Biomedicine, Biotechnology and Public Health and INIBICA, Cádiz, M. Carmen Durán-Ruiz (PI).
3. GLOBALCAJA COVID-19 Funds (May 26, 2020 to November 26, 2020). Monitoring COVID-19 infection in asymptomatic or mildly symptomatic healthcare workers at Hospital Nacional de Parapléjicos. Moreno-Luna R (PI).
4. CRUE-Santander Fondo Supera COVID19 (2020-2021). Multicenter project. Impact of SARS-CoV-2 on asymptomatic or mildly symptomatic healthcare workers. Identification of new biomarkers and pathogenic mechanisms. Moreno-Luna R (PI). In collaboration with the Department of Biomedicine, Biotechnology and Public Health and INIBICA, Cádiz, M. Carmen Durán-Ruiz (PI), and Research Group GE-06, Pathophysiology of Renal and Vascular Damage, IMIBIC, Córdoba, J. Antonio Moreno-Gutiérrez (PI).
WHERE WE HAVE PUBLISHED OUR SCIENTIFIC RESULTS IN THE LAST FIVE YEARS (Data updated through 2025)
Key: Title. Journal link. D1, Decile: top 10% of its category. Q, Quartile: Q1 = top 25%; Q2 = 25% to 50%; Q3 = 50% to 75%; Q4 = 75% to 100%. IF: Impact Factor.
1. Scientific Article: Vasculogenic potential of adipose tissue-derived stem cells from patients with chronic spinal cord injury and pressure injuries. Angiogenesis. 2025 Sep 10;28(4):48. https://link.springer.com/article/10.1007/s10456-025-10002-y D1/Q1; IF: 9.2
2. Literature Review: Multifaceted Pathophysiology and Secondary Complications of Chronic Spinal Cord Injury: Focus on Pressure Injury. Journal of Clinical Medicine. 2025 Feb 26;14(5):1556. https://www.mdpi.com/2077-0383/14/5/1556 Q1; IF: 3.3
3. Scientific Article: Unraveling the differential mechanisms of revascularization promoted by MSCs and ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia. Journal of Biomedical Science. 2024 Jul 15;31(1):71. https://link.springer.com/article/10.1186/s12929-024-01059-w D1/Q1; IF: 12.1
4. Scientific Article: Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps. International Forum of Allergy & Rhinology. 2024 Jul;14(7):1245-1248. https://doi.org/10.1002/alr.23327. D1/Q1; IF: 7.2
5. Scientific Article: Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients. International Journal of Biological Sciences. 2023;19(6):1664-1680. https://doi.org/10.7150/ijbs.78864. D1/Q1; IF: 10.5
6. Literature Review: Endocannabinoid signaling in oligodendroglia. Glia. 2023 Jan;71(1):91-102. https://onlinelibrary.wiley.com/doi/10.1002/glia.24180. Q1; IF: 8.1
7. Scientific Article: Assessment of endothelial colony-forming cells delivery routes in a murine model of critical limb-threatening ischemia using an optimized cell tracking approach. Stem Cell Research & Therapy. 2022 Jun 21;13(1):266. https://doi.org/10.1186/s13287-022-02943-8. Q1; IF: 8.1
8. Scientific Article: Supercritical impregnation of mango leaf extract into PLA 3D-printed devices and evaluation of their biocompatibility with endothelial cell cultures. Polymers. 2022 Jul 1;14(13):2706. https://doi.org/10.3390/polym14132706. Q1; IF: 5.0
9. Scientific Article: Post-COVID complications after pressure ulcer surgery in patients with spinal cord injury associate with creatine kinase upregulation in adipose tissue. Cells. 2022 Apr 9;11(8):1282. https://doi.org/10.3390/cells11081282. Q1; IF: 7.7
10. Scientific Article: Pro-angiogenic effects of natural antioxidants extracted from mango leaf, olive leaf, and red grape pomace over endothelial colony-forming cells. Antioxidants. 2022 Apr 27;11(5):851. https://doi.org/10.3390/antiox11050851. D1/Q1; IF: 7.7
11. Scientific Article: Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients. Molecular Therapy, Nucleic Acids. 2022 Sep 13;29:76-87. https://doi.org/10.1016/j.omtn.2022.06.006. Q1; IF: 10.1
12. Scientific Article:The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex vivo. Molecular Medicine. 2022 Apr 9;28(1):40. https://doi.org/10.1186/s10020-022-00465-w. Q1; IF: 6.4
13. Scientific Article: Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation. Journal of Neurochemistry. 2021 May 3. https://doi.org/10.1111/jnc.15381. Q1; IF: 5.5
14. Scientific Article: Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes. Molecular Neurobiology. 2021 Feb;58(2):689-702. https://doi.org/10.1007/s12035-020-02148-1. Q1; IF: 5.7
15. Scientific Article: Atherosclerotic pre-conditioning affects the paracrine role of circulating angiogenic cells ex vivo. International Journal of Molecular Sciences. 2020 Jul 24;21(15):5256. https://doi.org/10.3390/ijms21155256. Q1; IF: 6.2
16. Scientific Article: Identification of the initial molecular changes in response to circulating angiogenic cell-mediated therapy in critical limb ischemia. Stem Cell Research & Therapy. 2020 Mar 6;11(1):106. https://doi.org/10.1186/s13287-020-01591-0. Q1; IF: 8.1
17. Scientific Article: Revisiting CB1 cannabinoid receptor detection and the exploration of its interacting partners. Journal of Neuroscience Methods. 2020;337:108680. https://doi.org/10.1016/j.jneumeth.2020. Q3; IF: 3.0
18. Scientific Article: Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis. Journal of Personalized Medicine. 2020 Oct 21;10(4):183. https://doi.org/10.3390/jpm10040183. Q1; IF: 5.0
Main published results supporting our track record
Note: Selection of the 10 most relevant publications supporting the research line. Citation numbers are indicative and correspond to the date of page update.
1. Scientific Article: Vasculogenic potential of adipose tissue-derived stem cells from patients with chronic spinal cord injury and pressure injuries.
Angiogenesis. 2025;28(4):48.
https://link.springer.com/article/10.1007/s10456-025-10002-y
D1/Q1; IF: 9.2. Cited 3 times.
2. Scientific Article: Unraveling the differential mechanisms of revascularization promoted by MSCs and ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia.
Journal of Biomedical Science. 2024;31(1):71.
https://link.springer.com/article/10.1186/s12929-024-01059-w
D1/Q1; IF: 12.1. Cited 9 times.
3. Scientific Article: Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients.
International Journal of Biological Sciences. 2023;19(6):1664-1680.
https://doi.org/10.7150/ijbs.78864
D1/Q1; IF: 10.5. Cited 4 times.
4. Scientific Article: Assessment of endothelial colony-forming cells delivery routes in a murine model of critical limb-threatening ischemia using an optimized cell tracking approach.
Stem Cell Research & Therapy. 2022;13(1):266.
https://doi.org/10.1186/s13287-022-02943-8
Q1; IF: 8.1. Cited 4 times.
5. Scientific Article: Post-COVID complications after pressure ulcer surgery in patients with spinal cord injury associate with creatine kinase upregulation in adipose tissue.
Cells. 2022;11(8):1282.
https://doi.org/10.3390/cells11081282
Q1; IF: 7.7. Cited 6 times.
6. Scientific Article: Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks.
Nature Biomedical Engineering. 2017;1:0081.
https://doi.org/10.1038/s41551-017-0081
D1/Q1; IF: 29.8. Cited 97 times.
7. Scientific Article: Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling.
PNAS. 2014;111(28):10137-10142.
https://doi.org/10.1073/pnas.1405388111
D1/Q1; IF: 9.2. Cited 187 times.
8. Scientific Article: Human white adipose tissue vasculature contains endothelial colony-forming cells with robust in vivo vasculogenic potential.
Angiogenesis. 2013;16(4):735-744.
https://doi.org/10.1007/s10456-013-9350-0
D1/Q1; IF: 5.0. Cited 83 times.
9. Scientific Article: Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel.
Biomaterials. 2013;34:6785-6796.
https://doi.org/10.1016/j.biomaterials.2013.05.060
D1/Q1; IF: 14.4. Cited 250 times.
10. Scientific Article: Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells.
Angiogenesis. 2012;15(3):443-455.
https://doi.org/10.1007/s10456-012-9272-2
D1/Q1; IF: 5.0. Cited 129 times.
Note: These studies have received more than 700 citations worldwide, reflecting their scientific impact and their contribution to the advancement of this research line.
WHO WE COLLABORATE WITH
As of the end of 2025, PRMG maintains an active network of national and international collaborations aimed at strengthening the development of cell therapies, regenerative medicine, vascular pathophysiology, tissue bioengineering, and preclinical validation.
Boston Children’s Hospital / Harvard Medical School, Dr. Juan M. Melero-Martín’s Group
Scientific collaboration linked to the international trajectory of the Principal Investigator in the field of vascular bioengineering, endothelial progenitor cells, ECFC/MSC interaction, and the formation of human vascular networks.
This collaboration provides an important basis for the group’s current line of research in vasculogenesis, vascular regeneration, and the development of cellular strategies for tissue repair.
INIBICA / University of Cádiz, Dr. M.ª Carmen Durán-Ruiz’s Group
Collaboration in regenerative cell therapy, applied proteomics, and vascular pathophysiology.
This network has contributed to the development of studies on critical limb ischemia and the proteomic characterization of processes related to vascular damage.
RICORS / CIBER, Dr. Tomás Segura and Dr. Gemma Serrano’s Group
Participation in cooperative networks focused on the study of cerebrovascular diseases.
This collaboration connects PRMG’s vascular pathophysiology line with national biomedical research networks in stroke, vascular damage, and cerebrovascular disease.
Institute of Biomedicine of Seville / Virgen del Rocío University Hospital / Loyola University Andalusia / The Hospital for Sick Children, Toronto, Dr. Antonio Ordóñez and Dr. Israel Valverde’s Group
Strategic collaboration in vascular bioengineering, cardiovascular pathophysiology, tissue reconstruction, and experimental approaches based on human cells.
This collaboration integrates the expertise of Antonio Ordóñez and Israel Valverde in the development of advanced models for cardiovascular research and tissue repair, connecting national and international capabilities in regenerative medicine, bioengineering, and translational application.
This network is especially relevant for the development of ECFC/MSC cellular platforms derived from human adipose tissue, aimed at vascular repair, tissue reconstruction, and the preclinical development of advanced therapies.
Centro de Cirugía de Mínima Invasión Jesús Usón — Cáceres / TERAV+, Dr. Francisco Miguel Sánchez Margallo’s Group
Strategic collaboration aimed at the preclinical development of advanced cell therapies in vascular and tissue regeneration.
The alliance between PRMG and the Jesús Usón Minimally Invasive Surgery Center makes it possible to integrate the group’s expertise in ECFC/MSC cells derived from human adipose tissue with advanced capabilities in large animal models, experimental surgery, biomedical imaging, and preclinical validation.
This collaboration was the basis for joint integration into the Spanish Advanced Therapies Network, TERAV+, after an internal selection process in which the final application was favorably evaluated as a research group.
The collaboration is currently oriented toward the development of an ECFC/MSC platform with GMP-like adaptation, aligned with the regulatory requirements applicable to advanced therapy medicinal products and aimed at generating robust preclinical evidence in severe vascular disease, ischemia, revascularization, and vascular bioengineering.
HOW WE TAKE OUR RESEARCH BEYOND THE LABORATORY
PRMG’s work is not limited to the laboratory. We also seek to communicate our advances at scientific conferences, specialized meetings, and through the media, bringing research in regenerative medicine and cell therapies closer to professionals, patients, families, and society.
At scientific conferences and forums
Our work has been presented at national meetings related to regenerative medicine, cell therapies, spinal cord injury, chronic wounds, and vascular bioengineering.
Among the most notable participations are:
41st National Meeting of the Spanish Society of Paraplegia and 30th National ASELME Symposium
We presented the potential of human adipose tissue-derived cells as a basis for developing advanced therapy medicinal products aimed at vascular regeneration and pressure injury repair in patients with spinal cord injury.
Official program:
https://www.congresosparaplejia.com/_files/ugd/8dacde_6512c032413b437781...
19th National Meeting of Transplant Coordinators and Communication Professionals, National Transplant Organization
We participated in a lecture on the repair of organs and tissues through cell-based therapies, from classical bone marrow approaches to current advanced therapies.
Official program:
https://www.ont.es/wp-content/uploads/2024/01/Programa-TOLEDO-2024.pdf
In the media
Several regional and national media outlets have disseminated PRMG’s advances, helping to communicate the work carried out at Hospital Nacional de Parapléjicos in tissue repair, regenerative medicine, and cell therapies.
Main Press Appearances
Cell Therapies and Tissue Repair, 2024
News coverage on PRMG’s advances in cellular strategies for tissue repair and pressure injuries.
See press compilation
Peripheral Ischemia and Revascularization, 2024
News coverage on the study published in Journal of Biomedical Science, focused on the potential of adipose tissue-derived cells to promote revascularization in preclinical models of peripheral ischemia.
See press compilation
Pressure Injuries in Spinal Cord Injury, 2025
News coverage on the review published in Journal of Clinical Medicine, aimed at understanding why these injuries are particularly complex in people with spinal cord injury.
See press compilation
Vascular Regeneration from Adipose Tissue, 2025
News coverage on the work published in Angiogenesis, in which the group validates a protocol to obtain cells with regenerative potential from subcutaneous adipose tissue of patients with chronic spinal cord injury.
See press compilation
Radio
“It’s Worth Investigating”: Pressure Injuries
PRMG participated in the section “It’s Worth Investigating”, within the program Castilla-La Mancha at 8, on Radio Castilla-La Mancha.
In the interview, we explained the group’s objectives, the main results achieved in 2025, and the importance of investigating new strategies to treat pressure injuries, especially in people with reduced mobility or spinal cord injury.
Broadcast: October 22, 2025
Duration: 24 min 10 sec
Listen to the interview:
https://t.co/HGt9Enzxa4
Television
RTVE Castilla-La Mancha Report
The regional news program of RTVE Castilla-La Mancha dedicated a report to PRMG’s work in cell therapies and regenerative medicine for pressure injuries in spinal cord injury, showing an integrated view from the perspective of the patient, healthcare staff, and the research team.
Broadcast: Castilla-La Mancha News, December 16, 2025
PRMG segment: minute 9:40 to 13:00
Watch the full program:
https://www.rtve.es/play/videos/noticias-de-castilla-la-mancha/noticias-castilla-mancha-16-12-2025-informativo-castilla-mancha-noticias-castilla-mancha/16861067/