Pathophysiology and Regenerative Medicine

Pathophysiology and Regenerative Medicine (PRMG)

 

Team leader: Rafael Moreno-Luna, PhD

 

Our group focuses on the research of human stem and progenitor cells with therapeutic potential for tissue reconstruction and repair. Our goal is to design cell-based protocols to restore damaged tissues in patients with various pathologies, particularly emphasizing vascular bed repair to facilitate adjacent tissue repair/reconstruction.

 

To achieve this purpose, we adopt two complementary approaches. Firstly, we investigatethe pathophysiology of the wound to understand the underlying causes of tissue loss and the state of the patient cellular populations. This knowledge is essential to design effective and safe therapeutic intervention strategies. Secondly, based on preliminary data, we aim to develop effective and safe protocols for the regeneration and healing of these wounds.

 

One of our main objectives is to identify stem and progenitor cells residing in patients with spinal cord injury and pressure ulcers. Initially, we analyze how the pathophysiology of the wound affects the therapeutic potential of these cells. Once this data is obtained, our goal is to develop a strategy for the regeneration of wounds such as pressure ulcers in these or other patients. For this purpose, we employ a multidisciplinary approach to find molecular and cellular markers to understand and diagnose the course of the pathophysiology, as the basis for the design of regenerative therapies meeting the requirements of the Spanish Agency of Medicines and Medical Devices (AEMPS) for the subsequent application in clinical trials.

 

We strive to provide innovative and personalized solutions that promote the health and well-being of our patients through rigorous research and the practical application of regenerative medicine.

 

 

Group researchers:

 

~ Rafael Moreno Luna: (PI), Group Leader. R3 Certification (AEI) 2023.
~ Mario Martínez-Torija: Hemodialysis Nurse at the University Hospital of Toledo. Predoctoral Researcher.
~ Mª Ángeles Ruiz de Infante: Occupational Health Nurse Specialist at SPRL. Regional Coordination of the Occupational Risk Prevention Service, SESCAM.
~ Ángela Santos de la Mata: Graduate student/ R1.Scientific-Technical Activities Contract (Article 23 Royal Decree-Law 8/2022, April 5). Affiliated with the project funded by the Consejería Sanidad de CLM. PI: Rafael Moreno Luna.

 

 

Projects funding the group's research lines:

 

ACTIVE PROJECTS:
1- Regional (Public): SESCAM &Consejería Sanidad de CLM2022 (15/06/2023-01/01/2025) Ref.: MRTA/SLB1. Combined use of MSCs & ECFCs from adipose tissue from spinal cord injured patients for chronic wound repair/regeneration. Biosafety trial. Moreno-Luna R (PI). Total amount: 100.980€.
2- National (Public): Agencia Estatal de Investigación, AEI-2023(01/09/2023-31/09/2026) 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). Total amount: 187.500€.
3- Regional (Public): Agencia de Investigación e Innovación de Castilla-La Mancha, INNOCAM 2024 (2024-2027); Ref.: SBPLY/23/180225/000083. Combined therapy for pressure ulcer treatment in spinal cord injured patients. Preclinical study validation. Moreno-Luna R (PI). In collaboration with the Neuroinflammation group, Esteban Pedro F. (PI). Total amount: 126.000€.

 

COMPLETED PROJECTS:
1- National (Public): Instituto de Salud Carlos III, AES-2018(01/01/2019-31/03/2023) Ref.: PI18/00427. Preclinical study: Combined use of stem and endothelial progenitor cells derived from adipose tissue from spinal cord injury for repair / regeneration of pressure ulcers. Moreno-Luna R (PI).
2- European (Public): The European Proteomics Infrastructure Consortium(30/06/2021-30/06/2022) Ref.: EPIC-XS-0000212. Role of resident adipose tissue-derived stem & 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 Duran-Ruiz (PI).
3-Regional (Private): GOLBALCAJA_Fondos COVID19. (26/05/2020-26/11/2020). Monitoring of COVID-19 infection in asymptomatic or mildly symptomatic healthcare personnel (Hospital Nacional de Parapléjicos). Moreno-Luna R (PI).
4- National (Public): CRUE-Santander Fondo Supera COVID19 (01/10/2020-31/12/2021) Multicentric Project. Impact of SARS COV2 on Asymptomatic or Mildly Symptomatic Healthcare Personnel. 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 Duran-Ruiz (PI) and the Research Group GE-06 Renal Damage Pathophysiology.

 

 

Publications (last 5 years):

 

  • Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2024 Jan 24. doi: 10.1002/alr.23327. Q1/IF: 6,4.
  • Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients. Int J BiolSci. 2023 Mar 5;19(6):1664-1680. doi: 10.7150/ijbs.78864. Q1/IF: 10,52. Article selected to be the cover.
  • Endocannabinoid signaling in oligodendroglia. Glia. 2023 Jan;71(1): 91-102. doi: 10.1002/glia.24180. Q1/IF: 8,07.
  • Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients. Mol Ther Nucleic Acids. 2022 Sep 13;29:76-87. doi: 10.1016/j.omtn.2022.06.006.Q1/ IF: 10,18.
  • Supercritical Impregnation of Mango Leaf Extract into PLA 3D-Printed Devices and Evaluation of Their Biocompatibility with Endothelial Cell Cultures. Polymers (Basel). 2022 Jul 1;14(13):2706. doi: 10.3390/polym14132706.Q1/IF I: 5,00
  • Assessment of endothelial colony forming cells delivery routes in a murine model of critical limb threatening ischemia using an optimized cell tracking approach.Rojas-Torres M, Stem Cell Res Ther. 2022 Jun 21;13(1): 266. doi: 10.1186/s13287-022-02943-8. Q1/IF: 8,07.
  • Pro-Angiogenic Effects of Natural Antioxidants Extracted from Mango Leaf, Olive Leaf and Red Grape Pomace over Endothelial Colony-Forming Cells. Antioxidants (Basel). 2022 Apr 27;11(5):851. doi: 10.3390/antiox11050851. Q1/IF: 7,03.
  • 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. doi: 10.3390/cells11081282. Q1/IF: 7,77.
  • The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.Mol Med. 2022 Apr 9;28(1):40. doi: 10.1186/s10020-022-00465-w. Q1/IF: 6,35.
  • Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation. J Neurochem. 2021 Aug;158(3):640-656. doi: 10.1111/jnc.15381. Q1/IF: 5,55.
  • Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes. Mol Neurobiol. 2021 Feb;58(2):689-702. doi: 10.1007/s12035-020-02148-1. Q1/IF: 4,6
  • Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo. Int J Mol Sci. 2020 Jul 24;21(15):5256. doi: 10.3390/ijms21155256. Q1/IF: 5,92.
  • Revisiting CB1 cannabinoid receptor detection and the exploration of its interacting partners.J Neurosci Methods. 2020 May 1;337:108680. doi: 10.1016/j.jneumeth.2020.108680.Q2/IF: 2,25.
  • Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia.Stem Cell Res Ther. 2020 Mar 6;11(1):106. doi: 10.1186/s13287-020-01591-0.Q1/ IF: 8,07.
  • Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis. J Pers Med. 2020 Oct 21;10(4):183. doi: 10.3390/jpm10040183. Q1/ IF: 5,00.
  • Relationship between the endothelial dysfunction and the expression of the β1-subunit of BK channels in a non-hypertensive sleep apnea group. PLoS One. 2019 Jun 19;14(6):e0217138. doi: 10.1371/journal.pone.0217138. Q1/IF: 3,20.

 

 

Top 10 selected publications supporting main line of research

 

  1. Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients. Int J Biol Sci. 2023; 5;19(6):1664-1680. doi: 10.7150/ijbs.78864. Q1/IF: 10,52. Article selected for journal cover. *Moreno-Luna R, Last Author
  2. Post-COVID Complications after Pressure Ulcer Surgery in Patients with Spinal Cord Injury Associate with Creatine Kinase Upregulation in Adipose Tissue. Cells. 2022: 9;11(8):1282. doi: 10.3390/cells11081282. Q1/ IF: 7,77. *Moreno-Luna R, Last Author
  3. Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks.Nat Biomed Eng. 2017;1:0081. doi: 10.1038/s41551-017-0081.Q1/ IF: 29,8.
  4. Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling. Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10137-42. doi: 10.1073/pnas.1405388111.Q1/ IF: 9,2
  5. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia. Hypertension. 2014 Jul;64(1):165-71. Q1/ IF: 6,8 *Moreno-Luna R, CorrespondingAuthor
  6. Maternal body-mass index and cord blood circulating endothelial colony-forming cells.J Pediatr. 2014 Mar;164(3):566-571. doi: 10.1016/j.jpeds.2013.10.063. Q1/ IF: 4,04 *Moreno-Luna R, First Author.
  7. Human white adipose tissue vasculature contains endothelial colony-forming cells with robust in vivo vasculogenic potential. Angiogenesis. 2013 Oct;16(4):735-44.doi: 10.1007/s10456-013-9350-0.Q1/ IF: 14,04.*Moreno-Luna R, co-first Author.
  8. Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel. Biomaterials. 2013 Sep;34(28):6785-96. doi: 10.1016/j.biomaterials.2013.05.060. Q1/IF: 14,04
  9. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens. 2012 Dec;25(12):1299-304. Q2/ IF: 2,68. 296 vecescitado. *Moreno-Luna R, First Author.
  10. Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells.Angiogenesis. 2012 Sep;15(3):443-55. doi: 10.1007/s10456-012-9272-2. Q1/IF: 14,04.

 

 

Other lines of research (collaborations):

 

- Since 2019-present. Study of the therapeutic potential of stem cells and endothelial progenitors in preclinical models of peripheral arterial disease and critical limb ischemia between the Hospital Nacional de Parapléjicos in Toledo, SESCAM; PI Rafael Moreno-Luna from the Hospital Nacional de Parapléjicos and responsible for the collaboration, with the Regenerative Cell Therapy and Applied Proteomics group, Department of Biomedicine, Biotechnology, and Public Health and INIBICA, Cádiz, led by PI Mº Carmen Duran Ruiz.

 

- Since 2021-present. Design and study of experimental approaches based on the use of human-origin cells for tissue repair and/or reconstruction Institute of Biomedicine of Seville (IBiS), Spain, represented by Antonio Ordoñez, and Israel Valverde, Pediatric Cardiologist & Investigator in Cardiac MRI, 3D print & Bioprinting, Head of Pediatric Cardiology Section and researcher in the Cardiovascular Pathophysiology group

 

- Since 2022-present, Moreno-Luna R, Researcher in the RICORS Group on cerebrovascular diseases (stroke) in the consortium of biomedical research centers (CIBER), exp: RD21/0006/0002. Cerebrovascular Diseases Research Group. University Hospital of Albacete-SESCAM. PI: Tomás Segura Martín and Gemma Serrano.