The Effect of Sertoli Cells on Xenotransplantation and Allotransplantation of Ventral Mesencephalic Tissue in a Rat Model of Parkinson's Disease

Yun-Ting Jhao; Chuang-Hsin Chiu; Chien-Fu F Chen; Ta-Kai Chou; Yi-Wen Lin; Yu-Ten Ju; Shinn-Chih Wu; Ruoh-Fang Yan; Chyng-Yann Shiue; Sheau-Huei Chueh; Christer Halldin; Cheng-Yi Cheng; Kuo-Hsing Ma

doi:10.3390/cells8111420

The Effect of Sertoli Cells on Xenotransplantation and Allotransplantation of Ventral Mesencephalic Tissue in a Rat Model of Parkinson's Disease

Cells. 2019 Nov 11;8(11):1420. doi: 10.3390/cells8111420.

Authors

Affiliations

¹ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
² Department of Nuclear Medicine, Tri-Service General Hospital, Taipei 114, Taiwan.
³ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
⁴ Institute of Oral Biology, National Yang-Ming University, Taipei 112, Taiwan.
⁵ Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan.
⁶ Department of Nuclear Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
⁷ Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.
⁸ Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
⁹ Department of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan.

Abstract

Intra-striatal transplantation of fetal ventral mesencephalic (VM) tissue has a therapeutic effect on patients with Parkinson's disease (PD). Sertoli cells (SCs) possess immune-modulatory properties that benefit transplantation. We hypothesized that co-graft of SCs with VM tissue can attenuate rejection. Hemi-parkinsonian rats were generated by injecting 6-hydroxydopamine into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats or pigs (rVM or pVM), with/without a co-graft of SCs (rVM+SCs or pVM+SCs). Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small animal-positron emission tomography (PET) coupled with [¹⁸F] DOPA or [¹⁸F] FE-PE2I, respectively. Immunohistochemistry (IHC) examination was used to determine the survival of the grafted dopaminergic neurons in the striatum and to investigate immune-modulatory effects of SCs. The results showed that the rVM+SCs and pVM+SCs groups had significantly improved drug-induced rotational behavior compared with the VM alone groups. PET revealed a significant increase in specific uptake ratios (SURs) of [¹⁸F] DOPA and [¹⁸F] FE-PE2I in the grafted striatum of the rVM+SCs and pVM+SCs groups as compared to that of the rVM and pVM groups. SC and VM tissue co-graft led to better dopaminergic (DA) cell survival. The co-grafted groups exhibited lower populations of T-cells and activated microglia compared to the groups without SCs. Our results suggest that co-graft of SCs benefit both xeno- and allo-transplantation of VM tissue in a PD rat model. Use of SCs enhanced the survival of the grafted dopaminergic neurons and improved functional recovery. The enhancement may in part be attributable to the immune-modulatory properties of SCs. In addition, [¹⁸F]DOPA and [¹⁸F]FE-PE2I coupled with PET may provide a feasible method for in vivo evaluation of the functional integrity of the grafted DA cell in parkinsonian rats.

Keywords: Parkinson’s disease; positron emission tomography; sertoli cell; transplantation; ventral mesencephalic tissue.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Heterografts
Immunohistochemistry
Male
Mesencephalon / metabolism*
Mesencephalon / pathology
Mesencephalon / transplantation*
Parkinson Disease / diagnosis
Parkinson Disease / etiology
Parkinson Disease / metabolism
Parkinson Disease / therapy*
Positron-Emission Tomography
Rats
Sertoli Cells / metabolism*
T-Lymphocytes / immunology
T-Lymphocytes / metabolism
Transplantation, Heterologous