title: X-linked severe combined immunodeficiency (X-SCID) rats for xeno-transplantation and behavioral evaluation.
abstract: BACKGROUND
  To evaluate the in vivo function of human dopaminergic (DA) neurons, Parkinson's disease (PD) model rats made by the hemi-lateral injection of 6-hydroxydopamine (6-OHDA) are widely used as host animals. In the case of such xeno-transplantation, however, immunosuppression is needed for good survival of the grafted cells.
  
  
  METHODS
  In order to determine whether human mature neurons can survive in X-linked severe combined immunodeficiency (X-SCID) rats without immunosuppression, we grafted human embryonic stem cell (ESC)-derived DA neurons into the striatum of X-SCID rats. We next treated the X-SCID rats with 6-OHDA and grafted mouse fetal DA neurons or human induced pluripotent stem cell (iPSC)-derived DA neurons to examine whether these rats can be used as PD model rats.
  
  
  RESULTS
  X-SCID rats did not elicit immune responses against human ESC-derived DA neurons and consequently resulted in good survival of the cells without immunosuppression. Furthermore, 6-OHDA-lesioned X-SCID rats exhibited rotational behavior, which was recovered by grafting mouse fetal DA neurons or human iPSC-derived DA neurons.
  
  
  METHODS
  Immunosuppression by drugs such as Cyclosporine A requires daily injection, which is stressful for rats and moreover may cause renal or hepatic failure. Furthermore, blood levels of the drug may not be stable, which weakens the reliability of the data.
  
  
  CONCLUSIONS
  Our results provide a more accessible and reliable method to evaluate the in vivo function of human DA neurons, potentially offering a pre-clinical study for the application of pluripotent stem cells.
authors: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Bumpei
authors: B
authors: Samata
authors: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Tetsuhiro
authors: T
authors: Kikuchi
authors: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Yoshifumi
authors: Y
authors: Miyawaki
authors: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Asuka
authors: A
authors: Morizane
authors: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Tomoji
authors: T
authors: Mashimo
authors: Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Masato
authors: M
authors: Nakagawa
authors: Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors: Keisuke
authors: K
authors: Okita
authors: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Department of Biological Repair, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; Department of Neurosurgery, Clinical Neuroscience, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: jbtaka@cira.kyoto-u.ac.jp.
authors: Jun
authors: J
authors: Takahashi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival; D059290:Dopaminergic Neurons / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D053595:Embryonic Stem Cells / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D011699:Putamen / Q000503:physiopathology / Q000601:surgery; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains; D011923:Rats, Nude; D055647:Rats, Transgenic; D012399:Rotation; D014183:Transplantation, Heterologous; D053632:X-Linked Combined Immunodeficiency Diseases / Q000473:pathology / Q000503:physiopathology
chemical_list: D016627:Oxidopamine
keywords: 6-Hydroxydopamine; Dopaminergic neurons; Immune response; Parkinson's disease; Severe combined immunodeficiency rats; Xeno-transplantation