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Therapeutic cloning in individual parkinsonian mice

Abstract

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response.

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Figure 1: Behavioral and histological analyses of autologous grafts.
Figure 2: In vitro and in vivo studies addressing variability of dopamine neuron yield and in vivo survival among multiple ntES cell lines.

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Acknowledgements

We thank J.P.H. Burb ach (Rudoplph Magnus Institute, Utrecht), M. Smidt (Rudolph Magnus Institute, Utrecht), K. Rajewsky (The CBD Institute, Massachusetts), C. Lobe (University of Toronto, Canada) and M.A.S. Moore (Sloan-Kettering Institute, New York) for reagents, A.C.F. Perry for helpful discussions and M. Leversha for technical assistance. Supported by the US National Institute of Neurological Disorders and Stroke (R21NS44231 and R01NS052671), the Starr Tri-institutional Stem Cell Initiative, the Michael J. Fox Foundation for Parkinson's Research, the Michael W. McCarthy Foundation and an unrestricted grant from the Kinetics Foundation.

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Authors and Affiliations

Authors

Contributions

V.T. designed the experiments, performed some of the in vivo experiments and analysis, supervised the entire in vivo section of the work and contributed to the manuscript; M.T. performed all in vitro ES cell culture experiments and analyses; G.P. performed most of the in vivo experiments and analysis and contributed to the Supplementary Methods section; J.M. assisted with the immunohistochemistry and analysis of in vivo experiments; B.C. assisted with animal care and in vivo tests; G.A.-S. assisted with the in vivo experiments; S.W., E.M., H.O. and T.W. performed the fibroblast isolation and culture and the nuclear transfer and ES cell line derivation; T.W. also contributed to experimental design; L.S. designed the experiments and contributed to the manuscript.

Corresponding authors

Correspondence to Viviane Tabar or Lorenz Studer.

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Supplementary Figs. 1–3, Supplementary Tables 1 & 2, and Supplementary Methods (PDF 5338 kb)

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Tabar, V., Tomishima, M., Panagiotakos, G. et al. Therapeutic cloning in individual parkinsonian mice. Nat Med 14, 379–381 (2008). https://doi.org/10.1038/nm1732

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