Stem Cells Secretome and Biomaterials Biotechnology

We have previously validated the use of the secretome of Mesenchymal Stem Cells (MSCs) from different sources, including those derived from pluripotent stem cells (iMSCs), as a possible therapeutic tool in animal models of PD and SCI. Current work is focused on further developing these approaches by:
1) Establishment of standardized culturing methodologies of MSCs and iMSCs through the use of human platelet lysate (collaboration with STEMMATTERS), as well specific supplements that enhance the regenerative properties of stem cells secretome.
2) Developing targeted extracellular vesicles towards PD and SCI degenerating sites to control neuro-inflammatory processes and boost regeneration
3) On site secretome delivery systems for PD applicattions based on biodegradable nanoparticles
4) New hydrogel biodegradable based delivery systems for the on-site release of the secretome in SCI. For this purpose, different systems are currently being used particularly PEG-HEP hydrogels and self-assembling supramolecular systems, which are the topic of current collaborations between our team and the labs of Carsten Werner (IPF, Dresden, Germany) and Alvaro Mata (University of Nottingham, UK), respectively. Our in-house developed GG-GRGDS and mimetic-ligand gellan gum hydrogels are also being screened for the same purpose.. Still on this topic it is our objective to further pre-vascularize these hydrogels before its implantation, enabling simultaneously the reestablishment of the blood-brain or blood spinal cord barriers, respectively (collaboration with Ethan Lippmann at Vanderbilt University, Nashville, USA)
Still within this project we are also expanding the know-how that we have generated in SCI and PD, towards the application in traumatic brain (TBI) and peripheral nerve (PNI) injuries, respectively, with established collaborations with Elisa Zanier (MNRIF, Milan, Italy) and Xavier Navarro (UAB, Spain)

Funding Agency

FCT

Fundação La Caixa

Neuroscience Santa Casa Awards – Prize Melo e Castro

Project Reference

MC-18-2021 POCI-01-0145-FEDER-029206 LCF/PR/HR20/00249

Project Members

António J. Salgado

Principal Investigator Project Leader

Nuno A. Silva

Principal Investigator

Nuno Jorge Lamas

Clinician-Researcher

Nuno Sevivas

Clinician-Researcher

Belém Sampaio-Marques

Postdoctoral Researcher

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

Sandra Barata-Antunes

PhD Student

Tiffany S. Pinho

PhD Student

Sofia Serra

Research Technician

Main Project Outcomes

Prizes

Prize Melo e Castro for Spinal Cord Injury Research (2013, 2017, 2021); Prize Manetro Belard for Neurodegenerative Diseases (2019) Publications: A.G. Pinho, J.R. Cibrão, R. Lima, E.D. Gomes, S.C. Serra, J. Lentilhas-Graça, C. Ribeiro, S. Lanceros-Mendez, F.G. Teixeira, S. Monteiro, N.A. Silva, A.J. Salgado. “Immunomodulatory and Regenerative Effects of the Full and Fractioned Adipose Tis

R.C. Assunção-Silva, L. Pinto, A.J. Salgado. “Cell Transplantation and Secretome Based Strategies in Spinal Cord Injury Regenerative Medicine: From Basic Studies in Animal Models to Clinical Applications”. Medicinal Research Reviews, (2021), in press

C.R. Marques. J. Pereira-Sousa, F.G. Teixeira, R.A. Sousa, A. Teixeira-Castro, A.J. Salgado*. “Mesenchymal Stem Cells Secretome Protects Against Alpha-Synuclein-Induced Neurodegeneration in a Carnorhabiditis elegans Model of Parkinson’s Disease”. Cytotherapy, (2021), 23(10): 894-901.

J. Campos, S. Guerra-Gomes, S.C. Serra, G. Baltazar, J. F. Oliveira, F.G. Teixeira, A.J. Salgado. “Astrocyte Signaling Impacts the Effects of Human Bone Marrow Mesenchymal Stem Cells Secretome Application into the Hippocampus: A Proliferation and Morphometrical Analysis on Astrocytic Cell Populations”. Brain Research, (2020), 1732: 146700

F.G. Teixeira, H. Vilaça-Faria, A.V. Domingues, J. Campos, A.J. Salgado. “Preclinical Comparison of Stem Cells Secretome and Levodopa Application in a 6-OHDA Rat Model of Parkinson’s Disease”. Cells, (2020) 9(2): 315.

Mendes-Pinheiro, S.I. Anjo, B. Manadas, J.D. da Silva, A.M. Marote, L.A. Behie, F.G. Teixeira, A.J. Salgado. “Bone marrow mesenchymal stem cells’ secretome exerts neuroprotective effects in a Parkinson’s disease rat model”. Frontiers in Bioengineering and Biotechnology, (2019), 7: 294.

E.D. Gomes, S.C. Mendes, R.C. Assunção-Silva, F.G. Teixeira, A.O. Pires, S.I. Anjo, B. Manadas, H. Leite-Almeida, J.M. Gimble, N. Sousa, A.C. Lepore, N.A. Silva, A.J. Salgado. “Co-Transplantation of Adipose tissue-derived Stromal Cells and Olfactory Ensheating Cells for Spinal Cord Injury Repair”. STEM CELLS, (2018), 36(5): 696-708 .

F.G. Teixeira, M.M. Carvalho, K.M. Panchalingam, A.J. Rodrigues, B. Mendes-Pinheiro, S. Anjo, B. Manadas, L. Behie, N. Sousa, A.J. Salgado. “Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease”, (2017), Stem Cells Translational Medicine, 6(2): 634-646.