Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei.
Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source of many different cell types for cell-based gene and tissue therapies [1-3]. Nevertheless, if the full potential of cell lines derived from donor embryos is to be realised, the problem of donor-recipient tissue matching needs to be overcome. One approach, which avoids the problem of transplant rejection, would be to establish stem cell lines from the patient's own cells through therapeutic cloning [3,4]. Recent studies have shown that it is possible to transfer the nucleus from an adult somatic cell to an unfertilised oocyte that is devoid of maternal chromosomes, and achieve embryonic development under the control of the transferred nucleus [5-7]. Stem cells isolated from such a cloned embryo would be genetically identical to the patient and pose no risk of immune rejection. Here, we report the isolation of pluripotent murine stem cells from reprogrammed adult somatic cell nuclei. Embryos were generated by direct injection of mechanically isolated cumulus cell nuclei into mature oocytes. Embryonic stem (ES) cells isolated from cumulus-cell-derived blastocysts displayed the characteristic morphology and marker expression of conventional ES cells and underwent extensive differentiation into all three embryonic germ layers (endoderm, mesoderm and ectoderm) in tumours and in chimaeric foetuses and pups. The ES cells were also shown to differentiate readily into neurons and muscle in culture. This study shows that pluripotent stem cells can be derived from nuclei of terminally differentiated adult somatic cells and offers a model system for the development of therapies that rely on autologous, human pluripotent stem cells.
Munsie
M J
MJ
Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
Michalska
A E
AE
O'Brien
C M
CM
Trounson
A O
AO
Pera
M F
MF
Mountford
P S
PS
D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D005260:Female; D005855:Germ Layers / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D053652:Nuclear Transfer Techniques; D006080:Ovarian Follicle / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*