Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

• Published in: International journal of molecular sciences Vol. 19; no. 3; p. 870
• Main Authors: Cizkova, Dasa, Cubinkova, Veronika, Smolek, Tomas, Murgoci, Adriana-Natalia, Danko, Jan, Vdoviakova, Katarina, Humenik, Filip, Cizek, Milan, Quanico, Jusal, Fournier, Isabelle, Salzet, Michel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-03-2018; MDPI
• Subjects: Animals; Axons; Biological properties; Bone marrow; Cells, Cultured; Conditioning; Culture Media, Conditioned - pharmacology; Cytokines - genetics; Cytokines - metabolism; Dorsal root ganglia; Ganglia, Spinal - cytology; GAP-43 protein; Glial cells; In vitro methods and tests; inflammation; Interleukin 2; Interleukin 6; Life Sciences; Male; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Nerve Regeneration; Neuronal Outgrowth - drug effects; Neuronal-glial interactions; Neurons - drug effects; Population studies; Rats; Rats, Wistar; Recovery of function; regeneration; Rodents; Spinal cord injuries; Spinal Cord Injuries - therapy; spinal cord injury; Stem cell transplantation; Stem cells; stem cells-derived conditioned media; Stromal cells; Tumor necrosis factor-α; Viability; spinal cord injury; stem cells-derived conditioned media; inflammation; regeneration
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19030870

It was recently shown that the conditioned medium (CM) of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM) applied intrathecally (IT) for spinal cord injury (SCI) recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG) primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.