Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantation suitable for treatment of Parkinson’s disease?

Neural Regen Res 2013;8:1190-1200.

Yoon HH, Min J, Shin N, Kim YH, Kim JM, Hwang YS, Suh JKF, Hwang O, Jeon SR.

Abstract

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson’s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

Supplement:

It has been reported that dental papilla-derived stem cells have neural differentiation potential. Because they can be easily obtained from extracted teeth of children, they are free of ethical complications and can be potential source of stem cells to treat neurodegenerative diseases such as Parkinson’s disease. In this study, we compared the results of transplanted human brain-derived neural stem cells which are commercial stem cell line with those of early-stage human dental papilla-derived stem cells. This study, for the first time, tested the effects of transplantation of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells on hemi-parkinsonian rats.

When human dental papilla-derived stem cells were injected into rats, all rats died unexpectedly within 2 weeks after transplantation. Post mortem study showed that densely packed homogenous tumors were formed in the injection site.

Sang Ryong Jeon-1Figure 1.  The tumor tissue within transplanted area (left) and the the aspect of densely packed globular tumors (right) from the rats received human dental papilla-derived stem cells.

Based on the results of experiments, we concluded that early-stage human dental papilla-derived stem cells were not a suitable source for cell therapy of Parkinson’s disease although early-stage stem cells showed a high survival rate when they were transplanted into host tissue.

On the other hand, human brain-derived neural stem cells showed a potential to differentiate into the dopaminergic neuron, but no dopamine secretion was detected.

Sang Ryong Jeon -2Figure 2. (Left)microPET image of the rat that received the injection of human brain-derived neural stem cells. Deficiency of dopamine transporter activity shown in the lesion site on the right striatum is indicated by the red arrow. (Right)Positive tyrosine hydroxylase (dopamine specific marker) staining of the rat that received the injection of human brain-derived neural stem cells in lesion site (dotted area).

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