The effect of sertoli cells on xenotransplantation and allotransplantation of ventral mesencephalic tissue in a rat model of parkinson’s disease
Journal
Cells
Journal Volume
8
Journal Issue
11
Date Issued
2019-11-01
Author(s)
Jhao, Yun Ting
Chiu, Chuang Hsin
Chen, Chien Fu F.
Chou, Ta Kai
Lin, Yi Wen
Yan, Ruoh Fang
Shiue, Chyng Yann
Chueh, Sheau Huei
Halldin, Christer
Cheng, Cheng Yi
Ma, Kuo Hsing
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.
Subjects
Parkinson’s disease | Positron emission tomography | Sertoli cell | Transplantation | Ventral mesencephalic tissue
Other Subjects
allotransplantation; animal cell; animal model; Article; behavioral test parameters; cell maturation; confocal microscopy; controlled study; corpus callosum; corpus striatum; dopaminergic activity; human; human tissue; immunohistochemistry; immunomodulation; medial forebrain bundle; mesencephalic tissue; nonhuman; Parkinson disease; positron emission tomography; rat; Sertoli cell; xenotransplantation; animal; disease model; immunology; male; mesencephalon; metabolism; Parkinson disease; pathology; Sertoli cell; T lymphocyte; transplantation; xenograft
Publisher
MDPI
Type
journal article