Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation
Open Access
- 27 August 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (8), e69515
- https://doi.org/10.1371/journal.pone.0069515
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.Keywords
This publication has 102 references indexed in Scilit:
- Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord InjuryJournal of Neurotrauma, 2012
- Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cordBrain, 2012
- Effect of Vascular Endothelial Growth Factor Treatment in Experimental Traumatic Spinal Cord Injury: In Vivo Longitudinal AssessmentJournal of Neurotrauma, 2011
- Antioxidant Therapies for Acute Spinal Cord InjuryNeurotherapeutics, 2011
- MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinomaCarcinogenesis: Integrative Cancer Research, 2009
- Quantitative analysis by in vivo imaging of the dynamics of vascular and axonal networks in injured mouse spinal cordProceedings of the National Academy of Sciences of the United States of America, 2009
- Grafting of Human Bone Marrow Stromal Cells Into Spinal Cord InjurySpine, 2009
- MFG-E8 Regulates Microglial Phagocytosis of Apoptotic NeuronsJournal of Neuroimmune Pharmacology, 2008
- Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in RatsNeurochemical Research, 2007
- Axonal Remyelination by Cord Blood Stem Cells after Spinal Cord InjuryJournal of Neurotrauma, 2007