title: Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation.
abstract: Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived mesenchymal stem cells (BMSCs) is promising. Indeed, these cells possess interesting properties to modulate CNS environment and allow axon regeneration and functional recovery. Unfortunately, BMSC survival and differentiation within the host spinal cord remain poor, and these cells have been found to have various adverse effects when grafted in other pathological contexts. Moreover, paracrine-mediated actions have been proposed to explain the beneficial effects of BMSC transplantation after spinal cord injury. We thus decided to deliver BMSC-released factors to spinal cord injured rats and to study, in parallel, their properties in vitro. We show that, in vitro, BMSC-conditioned medium (BMSC-CM) protects neurons from apoptosis, activates macrophages and is pro-angiogenic. In vivo, BMSC-CM administered after spinal cord contusion improves motor recovery. Histological analysis confirms the pro-angiogenic action of BMSC-CM, as well as a tissue protection effect. Finally, the characterization of BMSC-CM by cytokine array and ELISA identified trophic factors as well as cytokines likely involved in the beneficial observed effects. In conclusion, our results support the paracrine-mediated mode of action of BMSCs and raise the possibility to develop a cell-free therapeutic approach.
authors.affiliation: GIGA-Neuroscience, Axonal Regeneration and Cephalic Pain Unit, University of Liege, Liege, Belgium.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Cantinieaux
authors.forename: Renaud
authors.initials: R
authors.lastname: Quertainmont
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Loïc
authors.initials: L
authors.lastname: Rossi
authors.forename: Thomas
authors.initials: T
authors.lastname: Wanet
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Gary
authors.initials: G
authors.lastname: Brook
authors.forename: Jean
authors.initials: J
authors.lastname: Schoenen
authors.forename: Rachelle
authors.initials: R
authors.lastname: Franzen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D005260:Female; D018836:Inflammation Mediators / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009048:Motor Skills; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D046509:Tissue Culture Techniques
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators