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.

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.

• Authors: Bumpei Samata, Tetsuhiro Kikuchi, Yoshifumi Miyawaki, Asuka Morizane, Tomoji Mashimo, Masato Nakagawa, Keisuke Okita, Jun Takahashi
• Journal: Journal of neuroscience methods (J Neurosci Methods) Vol. 243 Pg. 68-77 (Mar 30 2015) ISSN: 1872-678X [Electronic] Netherlands
• PMID: 25662444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Oxidopamine

Topics

• Animals
• Cell Culture Techniques
• Cell Survival
• Dopaminergic Neurons (pathology, physiology, transplantation)
• Embryonic Stem Cells (physiology)
• Humans
• Induced Pluripotent Stem Cells (physiology)
• Mice, Inbred C57BL
• Motor Activity (physiology)
• Oxidopamine
• Parkinsonian Disorders (pathology, physiopathology)
• Putamen (physiopathology, surgery)
• Rats, Inbred F344
• Rats, Mutant Strains
• Rats, Nude
• Rats, Transgenic
• Rotation
• Transplantation, Heterologous
• X-Linked Combined Immunodeficiency Diseases (pathology, physiopathology)