RRC ID 33285
著者 Samata B, Kikuchi T, Miyawaki Y, Morizane A, Mashimo T, Nakagawa M, Okita K, Takahashi J.
タイトル X-linked severe combined immunodeficiency (X-SCID) rats for xeno-transplantation and behavioral evaluation.
ジャーナル J Neurosci Methods
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.
NEW 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.
COMPARISON WITH EXISTING 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.
巻・号 243
ページ 68-77
公開日 2015-3-30
DOI 10.1016/j.jneumeth.2015.01.027
PII S0165-0270(15)00034-5
PMID 25662444
MeSH Animals Cell Culture Techniques Cell Survival Dopaminergic Neurons / pathology Dopaminergic Neurons / physiology Dopaminergic Neurons / transplantation* Embryonic Stem Cells / physiology Humans Induced Pluripotent Stem Cells / physiology Mice, Inbred C57BL Motor Activity* / physiology Oxidopamine Parkinsonian Disorders / pathology Parkinsonian Disorders / physiopathology* Putamen / physiopathology Putamen / surgery Rats, Inbred F344 Rats, Mutant Strains* Rats, Nude Rats, Transgenic Rotation Transplantation, Heterologous* X-Linked Combined Immunodeficiency Diseases* / pathology X-Linked Combined Immunodeficiency Diseases* / physiopathology
IF 2.214
引用数 7
WOS 分野 BIOCHEMICAL RESEARCH METHODS NEUROSCIENCES
リソース情報
ラット F344-Il2rgem2Kyo(strainID=979)