Adipose tissue derived stem cell secretome induces motor and histological gains after complete spinal cord injury in Xenopus laevis and mice

Rita C Assunção-Silva; Andreia Pinho; Jorge R Cibrão; Inês M Pereira; Susana Monteiro; Nuno A Silva; Jonas Campos; Ana L Rebelo; Gerhard Schlosser; Luisa Pinto; Abhay Pandit; António J Salgado

doi:10.1177/20417314231203824

Adipose tissue derived stem cell secretome induces motor and histological gains after complete spinal cord injury in Xenopus laevis and mice

J Tissue Eng. 2024 Feb 9:15:20417314231203824. doi: 10.1177/20417314231203824. eCollection 2024 Jan-Dec.

Authors

Rita C Assunção-Silva^{1

2

3}, Andreia Pinho^{1

2}, Jorge R Cibrão^{1

2}, Inês M Pereira^{1

2}, Susana Monteiro^{1

2}, Nuno A Silva^{1

2}, Jonas Campos^{1

2}, Ana L Rebelo⁴, Gerhard Schlosser⁴, Luisa Pinto^{1

2

3}, Abhay Pandit⁴, António J Salgado^{1

2}

Affiliations

¹ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
² ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
³ BnML - Behavioral and Molecular Lab, Braga, Portugal.
⁴ CÚRAM, SFI Research Center for Medical Devices, National University of Ireland, Galway, Ireland.

Abstract

Mesenchymal stem cell-based therapies have been studied for spinal cord injury (SCI) treatment due to their paracrine action upon damaged tissues. MSCs neuroregenerative role may relate to the contents of their secretome in anti-inflammatory cytokines and growth-permissive factors. We propose using the secretome of MSCs isolated from the adipose tissue-adipose tissue-derived stem cells (ASCs) as a cell-free based therapy for SCI. In vivo studies were conducted in two SCI models, Xenopus laevis and mice, after complete spinal cord transection. Our results on both models demonstrated positive impacts of ASC secretome on their functional recovery which were correlated with histopathological markers of regeneration. Furthermore, in our mice study, secretome induced white matter preservation together with modulation of the local and peripheral inflammatory response. Altogether, these results demonstrate the neuroregenerative and potential for inflammatory modulation of ASC secretome suggesting it as a good candidate for cell-free therapeutic strategies for SCI.

Keywords: Spinal cord injury; Xenopus laevis; adipose tissue derived stem cell; axonal growth; mouse model; neuroinflammation; regeneration; secretome.