Research Paper Volume 13, Issue 3 pp 4370—4387
Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation
- 1 Cell Therapy Center, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, China
- 2 Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, China
- 3 Shandong Research Center of Transplantation and Tissue, Jinan 250013, China
- 4 Jinan Dien Forensic Judical Appraisal Institute, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, China
Received: April 29, 2020 Accepted: September 19, 2020 Published: January 20, 2021
https://doi.org/10.18632/aging.202399How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Transplantation of mesenchymal stromal cells (MSCs) improves functional recovery in experimental models of spinal cord injury (SCI), but the mechanism is not fully understood. Activation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen-modifying enzyme, reportedly follows MSC transplantation in an SCI animal model. We investigated the regulation of PLOD2 expression and its potential contribution to the neuroprotective effects of adipose-derived stromal cells (ADSCs) following mechanical injury to neurons in vitro and SCI in vivo. ADSCs enhanced wound healing in vitro and promoted functional recovery after their implantation near injury sites in a rat SCI model. These effects correlated with upregulation of PLOD2, MAP2, NSE and GAP43, and downregulation of GFAP, which is indicative of improved neuronal survival and axonal regeneration as well as reduced glial scar formation. The neurorestorative effect of ADSCs was weakened after inhibition of PLOD2 expression. ADSCs appeared to induce PLOD2 upregulation via TGF-β1 secretion, as ADSC-mediated PLOD2 expression, neuronal survival, and functional recovery after SCI were largely prevented by SB431542, a TGF-(1 receptor inhibitor. These findings indicate that ADSCs reduce lesion size and promote functional recovery after SCI mainly through activation of a TGF-β1/P-Samd3/PLOD2 pathway in spinal cord neurons.
Abbreviations
MSCs: mesenchymal stromal cells; SCI: spinal cord injury; ADSCs: adipose -derived stromal cells; TGF-(1: transforming growth factor beta 1; MAP2: microtubule-associated protein 2; NSE: neuron-specific enolase; GAP43: growth-associated protein 43; GFAP: glial fibrillary acidic protein; PLOD2: procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2.