Jhao, Yun TingYun TingJhaoChiu, Chuang HsinChuang HsinChiuChen, Chien Fu F.Chien Fu F.ChenChou, Ta KaiTa KaiChouLin, Yi WenYi WenLinYU-TEN JUSHINN-CHIH WUYan, Ruoh FangRuoh FangYanShiue, Chyng YannChyng YannShiueChueh, Sheau HueiSheau HueiChuehHalldin, ChristerChristerHalldinCheng, Cheng YiCheng YiChengMa, Kuo HsingKuo HsingMa2023-04-102023-04-102019-11-012073-4409https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088206915&doi=10.3390%2fcells8111420&partnerID=40&md5=c74c82805fb542d628a6c9281896ec20https://scholars.lib.ntu.edu.tw/handle/123456789/630077Intra-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.enParkinson’s disease | Positron emission tomography | Sertoli cell | Transplantation | Ventral mesencephalic tissue[SDGs]SDG3Animals; Disease Models, Animal; Heterografts; Immunohistochemistry; Male; Mesencephalon; Parkinson Disease; Positron-Emission Tomography; Rats; Sertoli Cells; T-Lymphocytes; Transplantation, Heterologousallotransplantation; 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; xenograftjournal article10.3390/cells8111420317180582-s2.0-85088206915WOS:000502266700118https://api.elsevier.com/content/abstract/scopus_id/85088206915