Systemic human CD34(+) cells populate the brain and activate host mechanisms to counteract nigrostriatal degeneration

Regen Med. 2015;10(5):563-77. doi: 10.2217/rme.15.32.

Abstract

Aim: Here we investigated the neuroprotective potential of systemic CD34(+) human cord blood cells (hCBCs) in a 6-hydroxydopamine rat model of Parkinson's disease.

Methods: Purified CD34(+) hCBCs were intravenously administered to rats subjected to 6-hydroxydopamine 24 h earlier, and behavioral and immunohistological analysis performed.

Results: CD34(+) hCBC administration significantly prevented host nigrostriatal degeneration inducing behavioral recovery in treated rats. Although donor hCBCs did not differentiate into neural phenotypes, they stimulated the production of new neuroblasts and angiogenesis, and reduced gliosis in recipient animals. Importantly, surviving donor hCBCs were identified, and their tissue distribution pattern correlated with the observed therapeutic effects.

Conclusion: Peripherally applied CD34(+) hCBCs can migrate into brain tissues and elicit host-based protective mechanisms to support the survival of midbrain dopamine neurons.

Keywords: 6-OHDA; CD34+ mononuclear cells; Parkinson's disease; angiogenesis; cord blood; neurogenesis; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Brain / pathology
  • Cell Differentiation
  • Cell Line
  • Cell Movement
  • Cord Blood Stem Cell Transplantation*
  • Disease Models, Animal
  • Dopamine / chemistry
  • Fetal Blood / cytology*
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Male
  • Mesencephalon / cytology
  • Neovascularization, Pathologic
  • Nerve Degeneration / pathology
  • Neurons / cytology
  • Oxidopamine / chemistry
  • Parkinson Disease / therapy*
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Stem Cells / cytology
  • Substantia Nigra / cytology
  • Tissue Distribution

Substances

  • Antigens, CD34
  • Oxidopamine
  • Dopamine