Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats

CNS Neurosci Ther. 2020 Jan;26(1):55-65. doi: 10.1111/cns.13149. Epub 2019 May 13.

Abstract

Background: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment.

Methods: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis.

Results: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months.

Conclusions: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be a new potential strategy for the cell replacement therapy in PD.

Keywords: Parkinson's disease; inflammatory; microglia; neural stem cells; nuclear receptor-related factor 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine
  • Animals
  • Behavior, Animal
  • Calcium-Binding Proteins / genetics
  • Cell Differentiation
  • Corpus Striatum / surgery
  • Dopaminergic Neurons / transplantation
  • Encephalitis / therapy
  • Female
  • Genetic Therapy / methods*
  • Hydroxydopamines
  • Male
  • Microfilament Proteins / genetics
  • Microglia / transplantation*
  • Neural Stem Cells / transplantation*
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / biosynthesis
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / psychology
  • Parkinsonian Disorders / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation / methods*

Substances

  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Hydroxydopamines
  • Microfilament Proteins
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Amphetamine