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

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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

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Abbreviations

PD:

Parkinson’s disease

MSCs:

Mesenchymal stem cells

BMSCs:

Bone marrow-derived mesenchymal stem cells

DAT:

Dopamine transporter

6-OHDA:

6-hydroxydopamine

FP-CIT:

F-18 fluoropropylcarbomethoxyiodophenylnortropane

SD:

Sprague–Dawley

PBS:

Phosphate buffered saline

FWHM:

Full width half maximum

ROIs:

Regions of interest

SPM:

Statistical parametric mapping

TBS:

Tris-buffered saline

TH:

Tyrosine hydroxylase

F-18 FDOPA:

6-[F-18]-fluoro-L-4-dihydroxyphenylalanine

GDNF:

Glial-cell-line-derived neurotrophic factor

BDNF:

Brain-derived neurotrophic factor

CNTF:

Ciliary neurotrophic factor

ECM:

Extracellular matrix proteins

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Acknowledgments

The scientific guarantor of this publication is Joon-Kee Yoon. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study has received funding by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2011-0007935). No complex statistical methods were necessary for this paper.

Ethical Committee

The Care of Experimental Animals Committee of Ajou University School of Medicine approved all experimental procedures.

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Correspondence to Young-Sil An.

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Park, B., Kim, J., Lee, K. et al. 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 25, 1487–1496 (2015). https://doi.org/10.1007/s00330-014-3549-3

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Keywords

  • F-18 FP-CIT
  • Positron-emission tomography
  • Parkinson’s disease
  • Stem cell
  • Rat