Int J Stem Cells.  2014 May;7(1):43-47.

In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC) in the YAC128 Model of Huntington's Disease

• Jeon I
• Choi C
• Lee N
• Im W
• Kim M
• Oh SH
• Park IH
• Kim HS
• Song J

Abstract

Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can provide immense opportunities to model human diseases, which may lead to develop novel therapeutics. Huntington's disease (HD) is a devastating neurodegenerative genetic disease, with no available therapeutic options at the moment. We recently reported the characteristics of a HD patient-derived iPSC carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural precursors into the striatum of YAC128 mice bilaterally and observed a significant behavioral improvement in the grafted mice. Interestingly, the transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons efficiently, but no EM48-positive protein aggregates were detected at 12 weeks after transplantation. Taken together, these results indicate no HD pathology was developed from the grafted cells, or no transmission of HD pathology from the host to the graft occurred at 12 weeks post-transplantation.

Keyword

Huntington's disease (HD); Induced pluripotent stem cells (iPSCs); YAC128 transgenic mice; GABAergic neurons; Aggregate formation

MeSH Terms

Animals
GABAergic Neurons
Humans
Huntington Disease*
Induced Pluripotent Stem Cells
Mice
Mice, Transgenic
Neurons
Pathology
Pluripotent Stem Cells*
Transplants

Figure

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  Fig. 1. Pathological features of YAC128 transgenic mice. Expression of DARPP-32 (A, B) and EM48 (C, D) in YAC128 mice (A, C) and their littermates (B, D). Scale bar: 50 μm.

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  Fig. 2. Behavioral improvement following transplantation of HD72-iPSC-NPC into YAC mice. Significant improvement of rotarod activity was observed in the transplanted group at as early as three weeks after transplantation. *denotes p<05 and **denotes p<001.

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  Fig. 3. Immunohostochemical analyses showing neuronal differentiation and pathology development from the transplanted HD72-iPSC-NPC. (A∼F) Formation of markers specific for Nestin (A), MAP2 (B), GAD6 (C), GABA (D), DARPP-32 (E), and SVP38 (F). Arrowheads indicate the co-localized cells. (G, H) Areas showing transplanted human cells do not co-localize with EM48 (G), or the host tissues expressing EM48 but devoid of transplanted human cells (H). (I) Co-localization of EM48 in the DARPP-32-positive cells. Asterisks indicate the co-localized cells. Scale bar: 50 μm.

Reference

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