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

被引：51
作者：
Cizkova, Dasa [1 ,2 ,3 ]
Cubinkova, Veronika [1 ]
Smolek, Tomas [1 ]
Murgoci, Adriana-Natalia [1 ,2 ,3 ]
Danko, Jan [2 ]
Vdoviakova, Katarina [2 ]
Humenik, Filip [2 ]
Cizek, Milan [4 ]
Quanico, Jusal [3 ]
Fournier, Isabelle [3 ]
Salzet, Michel [3 ]
机构：
[1] Slovak Acad Sci, Inst Neuroimmunol, Dubrayska Cesta 9, Bratislava 84510, Slovakia
[2] Univ Vet Med & Pharm Kosice, Dept Anat Histol & Physiol, Komenskeho 73, Kosice 04181, Slovakia
[3] Univ Lille, INSERM, Lab Proteom Reponse Inflammatoire & Spectromet, U 1192, F-59000 Lille, France
[4] Univ Vet Med & Pharm Kosice, Dept Epizootol & Parasitol, Komenskeho 73, Kosice 04181, Slovakia
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 03期
关键词：
spinal cord injury; inflammation; regeneration; stem cells-derived conditioned media; STEM-CELLS; CLINICAL-TRIALS; TROPHIC FACTORS; REGENERATION; EXPRESSION; PLASTICITY; REPAIR; WINDOW; BRAIN; PHASE;
D O I：
10.3390/ijms19030870
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 TNF alpha when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.
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页数：13
相关论文
共 33 条
[1]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[2]  
Cizkova D, 1997, PHYSIOL RES, V46, P487
[3]   Modulation properties of factors released by bone marrow stromal cells on activated microglia: an in vitro study [J].
Cizkova, Dasa ;
Devaux, Stephanie ;
Le Marrec-Croq, Francoise ;
Franck, Julien ;
Slovinska, Lucia ;
Blasko, Juraj ;
Rosocha, Jan ;
Spakova, Timea ;
Lefebvre, Christophe ;
Fournier, Isabelle ;
Salzet, Michel .
SCIENTIFIC REPORTS, 2014, 4
[4]   Alterations of protein composition along the rostro-caudal axis after spinal cord injury: proteomic, in vitro and in vivo analyses [J].
Cizkova, Dasa ;
Le Marrec-Croq, Francoise ;
Franck, Julien ;
Slovinska, Lucia ;
Grulova, Ivana ;
Devaux, Stephanie ;
Lefebvre, Christophe ;
Fournier, Isabelle ;
Salzet, Michel .
FRONTIERS IN CELLULAR NEUROSCIENCE, 2014, 8
[5]   Repetitive Intrathecal Catheter Delivery of Bone Marrow Mesenchymal Stromal Cells Improves Functional Recovery in a Rat Model of Contusive Spinal Cord Injury [J].
Cizkova, Dasa ;
Novotna, Ivana ;
Slovinska, Lucia ;
Vanicky, Ivo ;
Jergova, Stanislava ;
Rosocha, Jan ;
Radonak, Jozef .
JOURNAL OF NEUROTRAUMA, 2011, 28 (09) :1951-1961
[6]   Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat [J].
Daša Čížková ;
Ján Rosocha ;
Ivo Vanický ;
Stanislava Jergová ;
Milan Čížek .
Cellular and Molecular Neurobiology, 2006, 26 (7) :1167-1180
[7]   Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair [J].
Devaux, Stephanie ;
Cizkova, Dasa ;
Quanico, Jusal ;
Franck, Julien ;
Nataf, Serge ;
Pays, Laurent ;
Hauberg-Lotte, Lena ;
Maass, Peter ;
Kobarg, Jan H. ;
Kobeissy, Firas ;
Meriaux, Celine ;
Wisztorski, Maxence ;
Slovinska, Lucia ;
Blasko, Juraj ;
Cigankova, Viera ;
Fournier, Isabelle ;
Salzet, Michel .
MOLECULAR & CELLULAR PROTEOMICS, 2016, 15 (08) :2641-2670
[8]   Protection in Animal Models of Brain and Spinal Cord Injury with Mild to Moderate Hypothermia [J].
Dietrich, W. Dalton ;
Atkins, Coleen M. ;
Bramlett, Helen M. .
JOURNAL OF NEUROTRAUMA, 2009, 26 (03) :301-312
[9]   Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials [J].
Fawcett, J. W. ;
Curt, A. ;
Steeves, J. D. ;
Coleman, W. P. ;
Tuszynski, M. H. ;
Lammertse, D. ;
Bartlett, P. F. ;
Blight, A. R. ;
Dietz, V. ;
Ditunno, J. ;
Dobkin, B. H. ;
Havton, L. A. ;
Ellaway, P. H. ;
Fehlings, M. G. ;
Privat, A. ;
Grossman, R. ;
Guest, J. D. ;
Kleitman, N. ;
Nakamura, M. ;
Gaviria, M. ;
Short, D. .
SPINAL CORD, 2007, 45 (03) :190-205
[10]   Overcoming inhibition in the damaged spinal cord [J].
Fawcett, JW .
JOURNAL OF NEUROTRAUMA, 2006, 23 (3-4) :371-383
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