Therapeutic effect of human amniotic epithelial cell transplantation into the lateral ventricle of hemiparkinsonian rats.
BACKGROUND
Human amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons. Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.


METHODS
The Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group. Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.


RESULTS
The rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P < 0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P < 0.01). Tyrosine hydroxylase (TH) positive cells in the substantia nigra of the HAEC group and the NS group were decreased compared to the untreated group (P < 0.01). Dopamine and DOPAC levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.05). Homovanillic acid (HVA) levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.01). In addition dopamine, DOPAC, and HVA levels in the striatum and dopamine levels in the cerebrospinal fluid of the HAECs group and the NS group were decreased compared to the untreated group (P < 0.05).


CONCLUSIONS
Human amniotic epithelial cells could be used to ameliorate the rotational asymmetry induced by apomorphine of the PD models. This could have been due to the increased content of dopamine and its metabolic products, DOPAC and HVA, in the striatum in the PD models.
Yang
Xin-xin
XX
Department of Neurology, First Affiliated Hospital of SooChow University, Suzhou, Jiangsu 215006, China.
Xue
Shou-ru
SR
Dong
Wan-li
WL
Kong
Yan
Y
D000650:Amnion / Q000166:cytology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016627:Oxidopamine; D001058:Apomorphine; D006719:Homovanillic Acid