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The Effect of Human Mesenchymal Stem Cells Derived from Wharton's Jelly in Spinal Cord Injury Treatment Is Dose-Dependent and Can Be Facilitated by Repeated Application.

Authors
  • Krupa, Petr1, 2
  • Vackova, Irena3
  • Ruzicka, Jiri4
  • Zaviskova, Kristyna5, 6
  • Dubisova, Jana7, 8
  • Koci, Zuzana9, 10
  • Turnovcova, Karolina11
  • Urdzikova, Lucia Machova12
  • Kubinova, Sarka13
  • Rehak, Svatopluk14
  • Jendelova, Pavla15, 16
  • 1 Department of Neurosurgery, Charles University, Medical Faculty and University Hospital Hradec Králové, Sokolska 581, 50005 Hradec Kralove, Czech Republic. [email protected] , (Czechia)
  • 2 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 3 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 4 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 5 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 6 Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006 Prague 5, Czech Republic. [email protected] , (Czechia)
  • 7 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 8 Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006 Prague 5, Czech Republic. [email protected] , (Czechia)
  • 9 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 10 Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006 Prague 5, Czech Republic. [email protected] , (Czechia)
  • 11 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 12 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 13 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 14 Department of Neurosurgery, Charles University, Medical Faculty and University Hospital Hradec Králové, Sokolska 581, 50005 Hradec Kralove, Czech Republic. [email protected] , (Czechia)
  • 15 Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic. [email protected] , (Czechia)
  • 16 Department of Neuroscience, Charles University, Second Faculty of Medicine, 15006 Prague 5, Czech Republic. [email protected] , (Czechia)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
May 17, 2018
Volume
19
Issue
5
Identifiers
DOI: 10.3390/ijms19051503
PMID: 29772841
Source
Medline
Keywords
License
Unknown

Abstract

Human mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) were used for the treatment of the ischemic-compression model of spinal cord injury in rats. To assess the effectivity of the treatment, different dosages (0.5 or 1.5 million cells) and repeated applications were compared. Cells or saline were applied intrathecally by lumbar puncture for one week only, or in three consecutive weeks after injury. Rats were assessed for locomotor skills (BBB, rotarod, flat beam) for 9 weeks. Spinal cord tissue was morphometrically analyzed for axonal sprouting, sparing of gray and white matter and astrogliosis. Endogenous gene expression (Gfap, Casp3, Irf5, Cd86, Mrc1, Cd163) was studied with quantitative Real-time polymerase chain reaction (qRT PCR). Significant recovery of functional outcome was observed in all of the treated groups except for the single application of the lowest number of cells. Histochemical analyses revealed a gradually increasing effect of grafted cells, resulting in a significant increase in the number of GAP43+ fibers, a higher amount of spared gray matter and reduced astrogliosis. mRNA expression of macrophage markers and apoptosis was downregulated after the repeated application of 1.5 million cells. We conclude that the effect of hWJ-MSCs on spinal cord regeneration is dose-dependent and potentiated by repeated application.

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