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Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat

Nature Neuroscience volume 5, pages 1271–1278 (2002)Cite this article

Abstract

Pluripotent or multipotent stem cells isolated from human embryos or adult central nervous system (CNS) may provide new neurons to ameliorate neural disorders. A major obstacle, however, is that the majority of such cells do not differentiate into neurons when grafted into non-neurogenic areas of the adult CNS. Here we report a new in vitro priming procedure that generates a nearly pure population of neurons from fetal human neural stem cells (hNSCs) transplanted into adult rat CNS. Furthermore, the grafted cells differentiated by acquiring a cholinergic phenotype in a region-specific manner. This technology may advance stem cell–based therapy to replace lost neurons in neural injury or neurodegenerative disorders.

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Figure 1: Morphological, immunocytochemical and electrophysiological characterization of primed and differentiated K048 fetal hNSCs in vitro.
Figure 2: Morphological and immunocytochemical characterization of primed and differentiated K054 fetal hNSCs in vitro.
Figure 3: Immunocytochemical characterization of FHL-primed K048 fetal hNSCs without further in vitro differentiation.
Figure 4: Neuronal differentiation and integration of primed fetal hNSCs one month post-grafting in various regions of brain and spinal cord of adult rats.
Figure 5: Confocal images of CAG-egfp-transduced fetal hNSCs without priming one month post-grafting in various regions of brain and spinal cord of adult rats.
Figure 6: Region-specific differentiation of neuron subtypes from primed fetal hNSCs after grafting in brain or spinal cord of adult rats.
Figure 7: Quantitative analyses of region-specific differentiation of neuronal subtypes from grafted fetal hNSCs in adult rat CNS from four separate experiments.

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Acknowledgements

The authors thank C.N. Svendsen and W.D. Willis for critical reading. We are also grateful to Y. Ye and Z. Chen for technical assistance, as well as to B.M. Walters for manuscript preparation. This work was supported by the John Sealy Memorial Endowment Fund (P.W.), Mission Connect of the Institute for Rehabilitation and Research Foundation (P.W.) and National Institute on Drug Abuse (L.M.H.).

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Authors and Affiliations

  1. Departments of Anatomy & Neurosciences, University of Texas Medical Branch, Galveston, 77555, Texas, USA

    Ping Wu, Yevgeniya I. Tarasenko, Yanping Gu & Richard E. Coggeshall

  2. Marine Biomedical Institute, University of Texas Medical Branch, Galveston, 77555, Texas, USA

    Ping Wu, Li-Yen M. Huang & Richard E. Coggeshall

  3. Departments of Physiology & Biophysics, University of Texas Medical Branch, Galveston, 77555, Texas, USA

    Li-Yen M. Huang

  4. Department of Radiation Oncology, University of Texas Medical Branch, Galveston, 77555, Texas, USA

    Yongjia Yu

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  1. Ping Wu
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Correspondence to Ping Wu.

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The University of Texas Medical Branch has submitted a patent application covering the method to produce region-specific neurons from human neural stem cells.

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Wu, P., Tarasenko, Y., Gu, Y. et al. Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat. Nat Neurosci 5, 1271–1278 (2002). https://doi.org/10.1038/nn974

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