Nuclear reprogramming: A key to stem cell function in regenerative medicine

Abstract

The goal of regenerative medicine is to restore form and function to damaged tissues. One potential therapeutic approach involves the use of autologous cells derived from the bone marrow (bone marrow-derived cells, BMDCs). Advances in nuclear transplantation, experimental heterokaryon formation and the observed plasticity of gene expression and phenotype reported in multiple phyla provide evidence for nuclear plasticity. Recent observations have extended these findings to show that endogenous cells within the bone marrow have the capacity to incorporate into defective tissues and be reprogrammed. Irrespective of the mechanism, the potential for new gene expression patterns by BMDCs in recipient tissues holds promise for developing cellular therapies for both proliferative and post-mitotic tissues.

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Figure 1: Schematic representation of the possible mechanisms of BMDC incorporation into non-haematopoietic tissues.
Figure 2: Reprogramming gene expression by nuclear transplantation (cloning) and by experimentally induced heterokaryon formation.
Figure 3: Reprogramming of bone marrow in non-haematopoietic tissues in vivo.

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Acknowledgements

We thank M. LaBarge, A. Palermo, R. Doyonnas, T. Brazelton, D. Spiegel and other members of the Blau laboratory for helpful discussions and critical reading of the manuscript. We especially thank C. Johansson for contributing the Purkinje cell image. We apologize to those whose important work we were not able to cover owing to space and reference limitations. J.P. is supported by an NIH training grant (HD 07249) as a postdoctoral fellow at Stanford University, and is a resident in the Division of Plastic and Reconstructive Surgery, Department of Surgery at the University of California, San Francisco (U.C.S.F.). H.M.B. is supported by: NIH grants AG 020961, AG 009521, HD 018179, Ellison AG-SS-0817, the McKnight Endowment Fund for Neuroscience and the Baxter Foundation.

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