Abstract

Therapeutic cloning, whereby somatic cell nuclear transfer (SCNT) is used to generate patient-specific embryonic stem cells (ESCs) from blastocysts cloned by nuclear transfer (ntESCs), holds great promise for the treatment of many human diseases. ntESCs have been derived in mice and cattle, but thus far there are no credible reports of human ntESCs. Here we review the recent literature on nuclear reprogramming by SCNT, including studies of gene expression, DNA methylation, chromatin remodeling, genomic imprinting and X chromosome inactivation. Reprogramming of genes expressed in the inner cell mass, from which ntESCs are derived, seems to be highly efficient. Defects in the extraembryonic lineage are probably the major cause of the low success rate of reproductive cloning but are not expected to affect the derivation of ntESCs. We remain optimistic that human therapeutic cloning is achievable and that the derivation of patient-specific ntESC lines will have great potential for regenerative medicine.

1. Xiangzhong Yang, Sadie L. Smith and X. Cindy Tian are at the Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Storrs, Connecticut 06269, USA. e-mail: xiangzhong.yang@uconn.edu
2. Harris A. Lewin is at the Department of Animal Sciences and Institute for Genomic Biology, University of Illinois, Urbana, Illinois 61801, USA.
3. Jean-Paul Renard is at the Unite Mixte de Recherche Biologie du Developpement et Reproduction, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
4. Teruhiko Wakayama is at the Center for Developmental Biology, RIKEN Kobe, 650-0047, Japan.

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