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Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats

Nature Biotechnology volume 16, pages 1040–1044 (1998)Cite this article

Abstract

Limited experimental access to the central nervous system (CNS) is a key problem in the study of human neural development, disease, and regeneration. We have addressed this problem by generating neural chimeras composed of human and rodent cells. Fetal human brain cells implanted into the cerebral ventricles of embryonic rats incorporate individually into all major compartments of the brain, generating widespread CNS chimerism. The human cells differentiate into neurons, astrocytes, and oligodendrocytes, which populate the host fore-, mid-, and hindbrain. These chimeras provide a unique model to study human neural cell migration and differentiation in a functional nervous system.

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Figure 1: Incorporation of human neural precursor cells into the developing rat brain, visualized by human-specific DNA in situ hybridization (dark nuclear labeling).
Figure 2: Human neural precursors grown for 6 weeks as monolayers in EGF- and FGF-containing media incorporated into the subventricular zone of the lateral ventricle and migrating into corpus callosum (cc), striatum (st), and cortex (co).
Figure 3: Morphological features of human neural precursors transplanted into the embryonic rat brain, visualized with a human-specific antibody to GSTπ.
Figure 4: Human oligodendrocytes derived from transplanted (A–C, G–H) EGF- and (D-F) EGF/FGF2-generated spheres incorporated into the brain of 7-week-old rats.
Figure 5: Astrocytic differentiation of the transplanted cells.
Figure 6: Human neurons incorporated into the rat brain.

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Acknowledgements

We thank Y. Maeda for providing the adenoviral vector and J. Trojanowski and P. Aubourg for the HO14 and ALDP antibodies, respectively. We would also like to thank John Rajan and his group for coordinating the tissue transfer and the Myelin Project for support to M.D.-D. and K.M.. Roberto Bruzzone, Kimberly Jones, and Bernard Rogister critically read the manuscript.

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Author notes

  1. Khalid Choudhary and Khalad Karram: These two authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke,

    Oliver Brüstle, Khalid Choudhary, Khalad Karram, Anita Hüttner & Ronald D.G. McKay

  2. National Institutes of Health , Bethesda, 20892-4092, MD

    Oliver Brüstle, Khalid Choudhary, Khalad Karram, Anita Hüttner & Ronald D.G. McKay

  3. Department of Neuropathology, University of Bonn Medical Center, Bonn, 53105, Germany

    Oliver Brüstle & Khalad Karram

  4. Unité de Neurovirologie et Régénération du Système Nerveux, Institut Pasteur, cedex 15, Paris, 75724, France

    Kerren Murray & Monique Dubois-Dalcq

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  1. Oliver Brüstle
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Correspondence to Oliver Brüstle.

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Brüstle, O., Choudhary, K., Karram, K. et al. Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats. Nat Biotechnol 16, 1040–1044 (1998). https://doi.org/10.1038/3481

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