Cell and Tissue Research

, Volume 348, Issue 3, pp 429–438

Transplantation of human umbilical cord blood cells mediated beneficial effects on apoptosis, angiogenesis and neuronal survival after hypoxic-ischemic brain injury in rats

  • Katja Rosenkranz
  • Sandra Kumbruch
  • Matthias Tenbusch
  • Katrin Marcus
  • Katrin Marschner
  • Rolf Dermietzel
  • Carola Meier
Regular Article

Abstract

Transplantation of human umbilical cord blood (hucb) cells in a model of hypoxic-ischemic brain injury led to the amelioration of lesion-impaired neurological and motor functions. However, the mechanisms by which transplanted cells mediate functional recovery after brain injury are largely unknown. In this study, the effects of hucb cell transplantation were investigated in this experimental paradigm at the cellular and molecular level. As the pathological cascade in hypoxic-ischemic brain injury includes inflammation, reduced blood flow, and neuronal cell death, we analyzed the effects of peripherally administered hucb cells on these detrimental processes, investigating the expression of characteristic marker proteins. Application of hucb cells after perinatal hypoxic-ischemic brain injury correlated with an increased expression of the proteins Tie-2 and occludin, which are associated with angiogenesis. Lesion-induced apoptosis, determined by expression of cleaved caspase-3, decreased, whereas the number of vital neurons, identified by counting of NeuN-positive cells, increased. In addition, we observed an increase in the expression of neurotrophic and pro-angiogenic growth factors, namely BDNF and VEGF, in the lesioned brain upon hucb cell transplantation. The release of neurotrophic factors mediated by transplanted hucb cells might cause a lower number of neurons to undergo apoptosis and result in a higher number of living neurons. In parallel, the increase of VEGF might cause growth of blood vessels. Thus, hucb transplantation might contribute to functional recovery after brain injury mediated by systemic or local effects.

Keywords

Cell transplantation Umbilical cord blood Neuronal survival Apoptosis Angiogenesis Rat (Wistar) 

Supplementary material

441_2012_1401_MOESM1_ESM.pdf (2.4 mb)
Fig. S1Expression of occludin in rat brains assessed by immunohistochemistry. Representative images of immunhistochemical staining of occludin (green), on P21 rat brains of animals of the following groups a sham, b lesion and c lesion+hucb (lesion plus additional application of hucb cells). Nuclei are labeled in blue (Hoechst staining a–c). Scale bar in (a) for (a–c) 50 μm (PDF 2484 kb)
441_2012_1401_MOESM2_ESM.pdf (5 kb)
Fig. S2Quantitative real time PCR analysis of rat VEGF mRNA expression. For determination of species origin of VEGF, quantitative real time PCR was performed with primers specific for rat VEGF. Analysis was performed at P9 and P21 in left hemispheres of rat brains of the following experimental groups: sham, sham+hucb, lesion and lesion+hucb. Significant differences of < 0.05 are indicated by *** (PDF 5 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Katja Rosenkranz
    • 1
  • Sandra Kumbruch
    • 2
  • Matthias Tenbusch
    • 3
  • Katrin Marcus
    • 1
  • Katrin Marschner
    • 4
  • Rolf Dermietzel
    • 2
  • Carola Meier
    • 5
  1. 1.Department of Functional ProteomicsRuhr-University BochumBochumGermany
  2. 2.Department of Neuroanatomy and Molecular Brain ResearchRuhr-University BochumBochumGermany
  3. 3.Department of Molecular and Medical VirologyRuhr-University BochumBochumGermany
  4. 4.Department of Gynecology and ObstetricsSt. Elisabeth-Hospital BochumBochumGermany
  5. 5.Department of Anatomy and Cell BiologySaarland UniversityHomburg/SaarGermany

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