Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats
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Neonatal hypoxia-ischemia (HI) is associated to cognitive and motor impairments and until the moment there is no proven treatment. The underlying neuroprotective mechanisms of stem cells are partially understood and include decrease in excitotoxicity, apoptosis and inflammation suppression. This study was conducted in order to test the effects of intracardiac transplantation of human dental pulp stem cells (hDPSCs) for treating HI damage. Seven-day-old Wistar rats were divided into four groups: sham-saline, sham-hDPSCs, HI-saline, and HI-hDPSCs. Motor and cognitive tasks were performed from postnatal day 30. HI-induced cognitive deficits in the novel-object recognition test and in spatial reference memory impairment which were prevented by hDPSCs. No motor impairments were observed in HI animals. Immunofluorescence analysis showed human-positive nuclei in hDPSC-treated animals closely associated with anti-GFAP staining in the lesion scar tissue, suggesting that these cells were able to migrate to the injury site and could be providing support to CNS cells. Our study evidence novel evidence that hDPSC can contribute to the recovery following hypoxia-ischemia and highlight the need of further investigation in order to better understand the exact mechanisms underlying its neuroprotective effects.
KeywordsDental pulp stem cells hDPSCs Neonatal hypoxia-ischemia Cellular therapy Memory
We thank The National Council for Scientific and Technological Development (CNPq), FAPERGS (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul) and Stem Cell Research Institute (SCRI) for their financial support.
- 22.Zhang X, Hirai M, Cantero S et al (2011) Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. J Cell Biochem 112:1206–1218. https://doi.org/10.1002/jcb.23042 CrossRefPubMedGoogle Scholar
- 29.Nicola FDC, Marques C, Odorcyk MR F et al (2017) Neuroprotector effect of stem cells from human exfoliated deciduous teeth transplanted after traumatic spinal cord injury involves inhibition of early neuronal apoptosis. Brain Res 1663:95–105. https://doi.org/10.1016/j.brainres.2017.03.015 CrossRefPubMedGoogle Scholar
- 30.de Paula S, Vitola a S, Greggio S et al (2009) Hemispheric brain injury and behavioral deficits induced by severe neonatal hypoxia-ischemia in rats are not attenuated by intravenous administration of human umbilical cord blood cells. Pediatr Res 65:631–635. https://doi.org/10.1203/PDR.0b013e31819ed5c8 CrossRefPubMedGoogle Scholar
- 32.van Velthoven CTJ, Kavelaars A, van Bel F, Heijnen CJ (2010) Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain Behav Immun 24:387–393. https://doi.org/10.1016/j.bbi.2009.10.017 CrossRefPubMedGoogle Scholar
- 41.Yasuhara T, Hara K, Maki M et al (2008) Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats. J Cereb Blood Flow Metab 28:1804–1810. https://doi.org/10.1038/jcbfm.2008.68 CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Park S, Koh SE, Maeng S et al (2011) Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity. Placenta 32:269–276. https://doi.org/10.1016/j.placenta.2010.12.027 CrossRefPubMedGoogle Scholar
- 43.Ten VS, Wu EX, Tang H et al (2004) Late measures of brain injury after neonatal hypoxia-ischemia in mice. Stroke 35:2183–2188. https://doi.org/10.1161/01.STR.0000137768.25203.df CrossRefPubMedGoogle Scholar