Patient-Specific Embryonic Stem Cells Derived from Human SCNT-Blastocysts





Woo Suk Hwang

College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea



Many human injuries and diseases result from defects in a single cell type. If defective cells could be replaced with appropriate stem cells, progenitor cells, or cells differentiated in vitro, it might be possible to treat disease and injury at the cellular level in the clinic, providing that immune rejection of transplanted cells could be avoided. By generating hESC from human NT-blastocysts in which the somatic cell nucleus comes from the individual patient, it might obviate the possibility of immune rejection if these cells were to be used for human treatment. Last year, we presented evidence that a human NT-hESC line [NT-hESC-1] was derived by transfer of the donors cumulus cell nucleus into her own enucleated oocyte. However, questions remained as to whether the cell line had a parthenogenetic origin. In addition, it was not known if NT-hESCs could be generated from NT procedures using nuclei from males, prepubescent girls, or post-menopausal women, or when using cell components from unrelated women. Finally, because NT-hESC-1 was grown on mouse feeders, with likely xenograft contamination, the utility of those cells is largely preclinical. In the current study, eleven new NT-hESCs have been established from skin cells donated by patients with diverse diseases, in which the nuclei were transferred into biologically-related or unrelated oocytes, then grown on human feeder cells, including the patient's own. With protocol improvements, NT-hESCs have been generated at remarkable rates (i.e.: 16.8 injected oocytes/NT-hESC line; or 13.8 oocytes/line excluding oocytes donated by women > 30 years old), regardless of nuclear donor sex, age or disease. All 11 NT-hESCs have been continuously cultured and cryopreserved. They are pluripotent, differentiated into multiple lineages, and chromosomally normal. All 11 NT-hESCs are identical matches with the respective donors DNA by fingerprinting. Major Histocompatibility Complex identity (MHC) of each of the 11 NT-hESCs with the patient's MHC showed immunological compatibility. Predictably successful derivations of patient-specific NT-hESCs requiring oocytes from a single woman donor, grown without animal cells, may advance stem cell transplantation as well as aid in elucidating the earliest processes during human development and these disease-carrying NT-hESC may also enable discovering complex disease mechanisms.




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