Improved dopamine transporter binding activity after bone marrow mesenchymal stem cell transplantation in a rat model of Parkinson's disease: small animal positron emission tomography study with F-18 FP-CIT

Eur Radiol. 2015 May;25(5):1487-96. doi: 10.1007/s00330-014-3549-3. Epub 2014 Dec 11.

Abstract

Objectives: We evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) in a model of Parkinson's disease (PD) using serial F-18 fluoropropylcarbomethoxyiodophenylnortropane (FP-CIT) PET.

Methods: Hemiparkinsonian rats were treated with intravenously injected BMSCs, and animals without stem cell therapy were used as the controls. Serial FP-CIT PET was performed after therapy. The ratio of FP-CIT uptake in the lesion side to uptake in the normal side was measured. The changes in FP-CIT uptake were also analyzed using SPM. Behavioural and histological changes were observed using the rotational test and tyrosine hydroxylase (TH)-reactive cells.

Results: FP-CIT uptake ratio was significantly different in the BMSCs treated group (n = 28) at each time point. In contrast, there was no difference in the ratio in control rats (n = 25) at any time point. SPM analysis also revealed that dopamine transporter binding activity was enhanced in the right basal ganglia area in only the BMSC therapy group. In addition, rats that received BMSC therapy also exhibited significantly improved rotational behaviour and preservation of TH-positive neurons compared to controls.

Conclusions: The therapeutic effect of intravenously injected BMSCs in a rat model of PD was confirmed by dopamine transporter PET imaging, rotational functional studies, and histopathological evaluation.

Key points: • Mesenchymal stem cells were intravenously injected to treat the PD rats • Dopamine transporter binding activity was improved after stem cell therapy • Stem cell therapy induced functional recovery and preservation of dopaminergic neurons • The effect of stem cells was confirmed by FP-CIT PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation*
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / metabolism
  • Parkinson Disease / therapy*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Tropanes*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Radiopharmaceuticals
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane