title: Nuclear transplantation, embryonic stem cells and the potential for cell therapy.
abstract: Nuclear transfer experiments in mammals have shown that the nucleus of an adult cell has the ability to direct the development of an entire organism, id est its genome is totipotent. However, these experiments did not conclusively demonstrate that the nuclei of terminally differentiated adult cells remain totipotent. It is possible that rare adult stem cells served as donors for the few surviving clones. To address this question, we have generated monoclonal mice from terminally differentiated lymphocytes that carry a single antigen receptor rearrangement in all tissues. Nuclear transfer technology may provide a powerful method for obtaining autologous cells for replacement therapy. We have demonstrated the feasibility of this concept by combining nuclear transfer with gene and cell therapy to treat the immune deficiency of Rag2 mutant mice, thus establishing a paradigm for 'therapeutic cloning'. Moreover, we will discuss the potential use of nuclear transfer to study the role of reversible genomic (epigenetic) modifications during tumorigenesis.
authors.affiliation: Whitehead Institute, Cambridge, MA, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
authors.forename: William M
authors.initials: WM
authors.lastname: Rideout
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D019976:Cloning, Organism; D004268:DNA-Binding Proteins / Q000172:deficiency; D044127:Epigenesis, Genetic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins; D053652:Nuclear Transfer Techniques; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology; D014182:Transplantation, Autologous
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2