1Department of Neurosurgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai   200240, China

2Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai   200040, China

3Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Fudan University, Shanghai   200032, China

4Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai   200031, China

Ying Xia☆, Doctor, Professor, Department of Neurosurgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai   200240, China Xia Y, Jiang CC, Ding ZL, Wang Y,  Xu B, Feng LY.Improvement of Parkinsonian behavior with co-grafts of Schwann cells and neural stem cells in the rat. Neural Regen Res 2008;3(1):5-9

Abstract

BACKGROUND: Due to the lack of autograft transplant rejection, Schwann cells (SCs) can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be induced to produce dopaminergic neurons. The therapeutic effects of co-grafts of SCs and neural stem cells (NSCs) deserves further study and verification in Parkinsonian animal models.

OBJECTIVE: To investigate the effects of Schwann cells and mesencephalic NSC co-grafts in Parkinsonian animal models on animal behavior and histology.

DESIGN: Randomized controlled experiment.

SETTING: Fudan University; Institute of Neuroscience, Chinese Academy of Sciences.

MATERIALS: The following animals were obtained from the Experimental Animal Center, Shanghai Institute for Biological Science, Chinese Academy of Sciences: 5 Sprague-Dawley rats, embryonic day (E) 13–16; 16 neonatal Sprague-Dawley rats, postnatal day 1–3; and 18 adult SD rats of both genders. Animal experimentation met animal ethical approval.

METHODS: The experiment was performed at the Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Fudan University from September 2005 to January 2007. The mesencephalic NSCs were obtained from the brains of SD rats at E 13–16, and SCs were harvested from the sciatic nerves of neonatal rats at day 1–3. Hemiparkinsonian rats (n =18) were selected for transplantation after estimating rotational behavior in response to apomorphine and were randomly assigned to three groups: control group, NSC group, and co-graft group. There were 6 rats in each group. Either phosphate buffered saline (PBS), NSCs, or SCs plus NSCs were transplanted into the right neostriatum of Parkinsonian rats, respectively.

MAIN OUTCOME MEASURES: ① Rotational behavior was induced by apomorphine (0.05 mg/kg, i.p.) 2, 4, 6, 8, and 10 weeks after transplantation, and the number of rotations were counted. ② Differentiation and survival of dopaminergic neurons in the right neostriatum were quantified by tyrosine hydroxylase immunohistochemistry 10 weeks after grafting.

RESULTS: All 18 Parkinsonian rats were included in the final analysis,without any loss. ①Rotation behavior and turning: Compared with the control group, the percent of apomorphine-induced rotations were significantly decreased (P < 0.01) in both the NSC group and co-graft group. ②Differentiation and survival of dopaminergic neurons in each group: TH-immunoreactive neurons were detected in the striatum of both the NSC group and co-graft group 10 weeks after transplantation. The neuronal volume, size of the nucleus, and neuronal numbers were larger in the co-graft group compared to the NSC group (P < 0.05).

CONCLUSION: SC and NSC co-grafts not only improve Parkinsonian behavior in rats, but also improve the survival of NSCs.

Key Words: Schwann cells; neural stem cells; Parkinson’s disease; co-graft

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