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Multilineage Potential of Homozygous Stem Cells Derived from Metaphase II Oocytes
Author(s) -
Lin Helen,
Lei JingQi,
Wininger David,
Nguyen MinhThanh,
Khanna Ruchi,
Hartmann Chris,
Yan WenLiang,
Huang Steve C.
Publication year - 2003
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.21-2-152
Subject(s) - biology , stem cell , embryonic stem cell , induced pluripotent stem cell , kosr , microbiology and biotechnology , immunology , adult stem cell , population , haematopoiesis , andrology , genetics , demography , sociology , gene , medicine
Abstract Human stem cells derived from human fertilized oocytes, fetal primordial germ cells, umbilical cord blood, and adult tissues provide potential cell‐based therapies for repair of degenerating or damaged tissues. However, the diversity of major histocompatibility complex (MHC) antigens in the general population and the resultant risk of immune‐mediated rejection complicates the allogenic use of established stem cells. We assessed an alternative approach, employing chemical activation of nonfertilized metaphase II oocytes for producing stem cells homozygous for MHC. By using F1 hybrid mice (H‐2‐B/D), we established stem cell lines homozygous for H‐2‐B and H‐2‐D, respectively. The undifferentiated cells retained a normal karyotype, expressed stage‐specific embryonic antigen‐1 and Oct4 , and were positive for alkaline phosphatase and telomerase. Teratomatous growth of these cells displayed the development of a variety of tissue types encompassing all three germ layers. In addition, these cells demonstrated the potential for in vitro differentiation into endoderm, neuronal, and hematopoietic lineages. We also evaluated this homozygous stem cell approach in human tissue. Five unfertilized blastocysts were derived from a total of 25 human oocytes, and cells from one of the five hatched blastocysts proliferated and survived beyond two passages. Our studies demonstrate a plausible “homozygous stem cell” approach for deriving pluripotent stem cells that can overcome the immune‐mediated rejection response common in allotransplantation, while decreasing the ethical concerns surrounding human embryonic stem cell research.

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