Novel Approaches in Nervous System Regenerative Medicine

Degeneration within the nervous system, either caused by trauma (e.g. Spinal Cord Injury – SCI), disease (e.g. Parkinson’s Disease – PD) or infection (e.g. Malaria), is a significant health problem that is yet to be efficiently tackled, due to the limited available treatment options. Having this in mind, the ReNEU team has a strong translational nature, being focused on the generation of innovative therapies for nervous system regenerative medicine with a particular focus on trauma related injuries and degeneration caused by disease or infection. For this purpose, we will use the present and future acquired know-how on the pathophysiology of these nervous system-related conditions to establish targeted regenerative medicine strategies that go beyond the current therapeutic options. This overall aim is based on research activities within on four main thematic areas:

(1) Stem Cells and Biomaterials Biotechnology, with a focus on the combinatory use of stem cells and their derived biological products (e.g. secretome) with biomimetic hydrogels to enhance regeneration.
(2) Molecular Therapies, with a focus on the study of new molecules that can enhance neuroprotection and/or trigger the intrinsic capacity of nervous system cells to initiate reparative processes.
(3) Enabling Technologies, with a focus on the development of innovative medical devices that respect the temporal dynamics of the injury/disease allowing a more effective application of the strategies established in 1,2.
(4) Basic mechanisms of injury/degeneration, with a focus on better understanding key aspects of the pathophysiology of CNS trauma and degeneration, allowing a more targeted development of the strategies referred in 1,2.

To successfully target these 4 main thematic areas, the team of ReNEU relays on strong collaboration among all its PhD and non-PhD members, who disclose a strong complementarity within basic, translation and clinical research. The expertise of this team is further complemented with key national/ international collaborations within these four main thematic areas.

Team Members

António J. Salgado

Principal Investigator
Team Coordinator

Nuno A. Silva

Principal Investigator

Pedro E. Ferreira

Principal Investigator

Nídia de Sousa

Assistant Researcher

Susana Monteiro

Assistant Researcher

Miguel F Gago

Clinician-Researcher

Nuno Jorge Lamas

Clinician-Researcher

Nuno Sevivas

Clinician-Researcher

Ana Marote

Postdoctoral Researcher

Sofia G. Meirinho

Postdoctoral Researcher

Andreia G. Pinho

PhD Student

Carla S. Sousa

PhD Student

Diogo Santos

PhD Student

Helena Cavaleiro

PhD Student

João Afonso

PhD Student

Jonas Campos

PhD Student

Jorge R. Cibrão

PhD Student

Miguel Ribeiro

PhD Student

Tiffany S. Pinho

PhD Student

Carlos Vedor

MSc Student

Filipa Antunes

MSc Student

Sofia Serra

Research Technician

Team Members

Projects

Success Story

Within the last ten years, ReNEU has established itself as a highly competitive team in the field of central nervous system regenerative medicine, where it:
1) Introduced the use of new hydrogel based biomaterials for SCI regeneration, PGGH, providing strong evidences that they could modulate the pathophysiology of the injury, and with this promote the recovery of rodent models of SCI
2) Characterized the secretome of MSCs, disclosed how it modulates CNS biology, and associated mechanisms that impacted neuronal ang glial survival, differentiation and axonal growth
3) Pioneered the use of cell-free therapies based on stem cells secretome for CNS regenerative medicine
4) Identified novel molecular and pharmaco therapies (e.g. LEV) aimed at SCI repair
5) Established brain-organoid biological systems to test new compounds targeting cerebral malaria.

This work has resulted in over 100 papers in some of the leading journals of the fields of biomaterials, stem cells and regenerative medicine, including Biomaterials, Small, Stem Cells, Stem Cells Translational Medicine, Advanced Functional Materials, American Journal of Sports Medicine, NPG Regenerative Medicine, Medicinal Research Reviews Progress in Neurobiology, Nature Microbiology and The Lancet Infectious Diseases. Additionally, the originality and ground-breaking nature of the research followed has originated 5 patents and was awarded with several distinctions including the prestigious Prize Melo e Castro for SCI research and the Gulbenkian Award for Cutting Edge Research in Life Sciences.
Further, ReNEU has also shown a strong capability to attract competitive funding from national and international bodies, from which the projects BIOHYBRID, BACLOFEN and DIAMOND4BRAIN, funded by EU/FP7, Wings for Life Spinal Cord Research Foundation and Fundación La Caixa, standout. The senior members of this team have obtained direct funding through more than 25 competitive grants over the last 10 years. Finally, the technical approaches developed by ReNEU also allowed to obtain direct funding from industrial partners.

Selected Research Outputs

Lentilhas-Graça, J., Santos, D. J., Afonso, J., Monteiro, A., Pinho, A. G., Mendes, V. M., . . . Silva, N. A. (2024). The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol. Frontiers in Immunology 15. doi:10.3389/fimmu.2024.1354479

Pinho, T. S., Cibrão, J. R., Silva, D., Barata-Antunes, S., Campos, J., Afonso, J. L., . . . Salgado, A. J. (2024). In vitro neuronal and glial response to magnetically stimulated piezoelectric poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)/cobalt ferrite (CFO) microspheres. Biomater Adv, 159, 213798. doi:10.1016/j.bioadv.2024.213798

Mendes-Pinheiro, B., Campos, J., Marote, A., Soares-Cunha, C., Nickels, S. L., Monzel, A. S., . . . Salgado, A. J. (2023). Treating Parkinson's Disease with Human Bone Marrow Mesenchymal Stem Cell Secretome: A Translational Investigation Using Human Brain Organoids and Different Routes of In Vivo Administration. Cells, 12(21). doi:10.3390/cells12212565

Silva, D., Schirmer, L., Pinho, T. S., Atallah, P., Cibrão, J. R., Lima, R., . . . Salgado, A. J. (2023). Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star-Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model. Adv Healthc Mater, 12(17), e2202803. doi:10.1002/adhm.202202803

Lima, R., Gomes, E. D., Cibrão, J. R., Rocha, L. A., Assunção-Silva, R. C., Rodrigues, C. S., . . . Silva, N. A. (2021). Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord. npj Regenerative Medicine, 6(1), 11. doi:10.1038/s41536-021-00121-7

Monteiro, S., Pinho, A. G., Macieira, M., Serre-Miranda, C., Cibrão, J. R., Lima, R., . . . Silva, N. A. (2020). Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord. J Neuroinflammation, 17(1), 282. doi:10.1186/s12974-020-01945-8

Silva, M., Calçada, C., Teixeira, M., Veiga, M. I., & Ferreira, P. E. (2020). Multigenic architecture of piperaquine resistance trait in Plasmodium falciparum. Lancet Infect Dis, 20(1), 26-27. doi:10.1016/s1473-3099(19)30689-9

2023: La Caixa Health Research Project “Wireless Neural Guidance Device for Spinal Cord Injury Regeneration”, Funding: 1 million euros.

Prize Melo e Castro for Spinal Cord Injury Research (2013, 2017, 2021), Total funding: 600K

Patent WO/2021/198909, Compositions for Treatment of Spinal Cord Injury, Methods and Uses Thereof