Cerebral function of bone marrow multipotent adult progenitor cells after transplantation in Parkinson's disease rat models

Transplant Proc. 2013 Mar;45(2):719-25. doi: 10.1016/j.transproceed.2012.09.120.

Abstract

Objective: This study sought to explore the mechanism of bone marrow-derived multipotent adult progenitor cell (MAPC) differentiation into neurons to restore functional deficits.

Methods: We were successfully established a rat model of Parkinson's disease (PD). MAPC were injected into the left striatum for cellular identification. At 3 months after the injection, behavioral tests, immunofluorescence reverse-transcriptase polymerase chain reaction (PCR) and electron microscopy were used to evaluate the rats.

Results: Compared with control animals, MAPC-derived dopaminergic neurons caused gradual, sustained behavioral restoration of dopamine-mediated motor asymmetry. Within 1 hour, the impaired gait of the rats in the MAPC group was improved compared with the control group (P < .05). After implantation, the MAPCs survived and differentiated into neuronlike cells in the substantia nigra and striatum including dopaminergic neurons. Real-time PCR revealed significantly higher dopamine-β-hydroxylase (1.64-fold increase), dopamine transporter (1.55-fold increase), and nerve growth factor (1.77-fold increase) mRNA levels in the MAPC group, suggesting that MAPC-derived neurons perform the function of dopaminergic neurons.

Conclusions: The immature synapses under electron microscopy show that MAPC-derived neurons have great potential in the reconstruction of the neural circuitry. Transplanted MAPCs develop spontaneously into dopaminergic neurons, which restore cerebral function and behavior in PD rat models.

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / transplantation*
  • Animals
  • Behavior, Animal
  • Bone Marrow Transplantation*
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Brain / surgery*
  • Cell Survival
  • Cells, Cultured
  • Disease Models, Animal
  • Dopamine beta-Hydroxylase / genetics
  • Dopamine beta-Hydroxylase / metabolism
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Dopaminergic Neurons / transplantation*
  • Female
  • Fluorescent Antibody Technique
  • Gait
  • Gene Expression Regulation
  • Injections
  • Male
  • Microscopy, Electron, Transmission
  • Motor Activity
  • Multipotent Stem Cells / metabolism
  • Multipotent Stem Cells / transplantation*
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation*
  • Neurogenesis*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / physiopathology
  • Parkinsonian Disorders / surgery*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Recovery of Function
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • RNA, Messenger
  • Nerve Growth Factor
  • Dopamine beta-Hydroxylase