Effects of human umbilical cord blood CD34+ cell transplantation in neonatal hypoxic-ischemia rat model

Brain Dev. 2019 Feb;41(2):173-181. doi: 10.1016/j.braindev.2018.08.007. Epub 2018 Sep 1.

Abstract

Perinatal brain injury can cause death in the neonatal period and lifelong neurodevelopmental deficits. Stem cell transplantation had been proved to be effective approach to ameliorate neurological deficits after brain damage. In this study we examine the effect of human umbilical cord blood CD34+ cells on model of neonatal rat hypoxic-ischemic brain damage and compared the neuroprotection of transplantation of CD34+ cells to mononuclear cells from which CD34+ cells isolated on neonatal hypoxic-ischemia rat model. Seven-day-old Sprague-Dawley rats were subjected to hypoxic-ischemic (HI) injury, CD34+ cells (1.5 × 104 cells) or mononuclear cells (1.0 × 106 cells) were transplanted into mice by tail vein on the 7 day after HI. The transplantation of CD34+ cells significantly improved motor function of rat, and reduced cerebral atrophy, inhibited the expression of glial fibrillary acidic protein (GFAP) and apoptosis-related genes: TNF-α, TNFR1, TNFR2, CD40, Fas, and decreased the activation of Nuclear factor kappa B (NF-κB) in damaged brain. CD34+ cells treatment increased the expression of DCX and lectin in ipsilateral brain. Moreover, the transplantation of CD34+ cells and MNCs which were obtained from the same amount of human umbilical cord blood had similar effects on HI. Our data demonstrated that transplantation of human umbilical cord blood CD34+ cells can ameliorate the neural functional defect and reduce apoptosis and promote nerve and vascular regeneration in rat brain after HI injury and the effects of transplantation of CD34+ cells were comparable to that of MNCs in neonatal hypoxic-ischemia rat model.

Keywords: CD34(+) cells; Cell therapy; Hypoxic-ischemic; Neuroprotection; Umbilical cord blood.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, CD34* / isolation & purification
  • Cord Blood Stem Cell Transplantation / methods*
  • Disease Models, Animal
  • Doublecortin Protein
  • Encephalitis / complications
  • Encephalitis / prevention & control
  • Humans
  • Hypoxia-Ischemia, Brain / complications
  • Hypoxia-Ischemia, Brain / therapy*
  • Rats, Sprague-Dawley

Substances

  • Antigens, CD34
  • Dcx protein, mouse
  • Dcx protein, rat
  • Doublecortin Protein