Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques

J Clin Invest. 2013 Jan;123(1):272-84. doi: 10.1172/JCI62516. Epub 2012 Dec 3.

Abstract

A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Cell- and Tissue-Based Therapy / methods*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / transplantation*
  • Gene Expression Regulation
  • Integrin alpha6beta4 / biosynthesis
  • Macaca fascicularis
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Parkinsonian Disorders / diagnostic imaging
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / therapy*
  • Positron-Emission Tomography
  • Radiography
  • Transplantation, Autologous

Substances

  • Antigens, Differentiation
  • Integrin alpha6beta4