Producing primate embryonic stem cells by somatic cell nuclear transfer.
Derivation of embryonic stem (ES) cells genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing concerns regarding rejection by the host immune system. However, the concept has only been achieved in the mouse, whereas inefficient reprogramming and poor embryonic development characterizes the results obtained in primates. Here, we used a modified SCNT approach to produce rhesus macaque blastocysts from adult skin fibroblasts, and successfully isolated two ES cell lines from these embryos. DNA analysis confirmed that nuclear DNA was identical to donor somatic cells and that mitochondrial DNA originated from oocytes. Both cell lines exhibited normal ES cell morphology, expressed key stem-cell markers, were transcriptionally similar to control ES cells and differentiated into multiple cell types in vitro and in vivo. Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES cells and demonstrate proof-of-concept for therapeutic cloning in primates.
Byrne
J A
JA
Oregon National Primate Research Center, Oregon Health & Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA.
Pedersen
D A
DA
Clepper
L L
LL
Nelson
M
M
Sanger
W G
WG
Gokhale
S
S
Wolf
D P
DP
Mitalipov
S M
SM
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D053652:Nuclear Transfer Techniques; D009928:Organ Specificity; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
D004272:DNA, Mitochondrial