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Allogeneic Transplantation of Genetically Modified Primate Embryonic Stem Cells
Author(s) -
Asano T,
Hanazono Y,
Sasaki K,
Ueda Y,
Hasegawa M,
Ageyama N,
Terao K,
Kitano Y,
Momoeda M,
Ozawa K,
Harii K
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.abstractbi.x
Subject(s) - biology , embryoid body , embryonic stem cell , stem cell , transplantation , fetus , genetic enhancement , immunology , microbiology and biotechnology , viral vector , haematopoiesis , virology , andrology , gene , adult stem cell , medicine , genetics , pregnancy , recombinant dna
Aim: To examine the efficacy and safety of human embryonic stem (ES) cell‐based therapies, allogeneic transplantation of monkey ES cells would be useful. We transplanted genetically marked monkey ES cells into the allogeneic fetus. Methods and Results: Cynomolgus ES cells were transduced once using a simian immunodeficiency virus‐based lentivirus vector encoding the GFP gene driven by the CMV promoter at 1, 10 and 100 transducing units per cell. Five days posttransduction, 60, 80 and 90% of the cells expressed GFP, respectively, and the expression levels were stable for 5 months. GFP expression was still observed after embryoid‐body formation. The gene‐marked ES cells were transplanted into the cynomolgus fetus in the abdominal cavity (n = 2) or liver (n = 1) after the first trimester. The fetuses were delivered 1 month posttransplantation. Transplanted cell progeny were detected (∼1%) in multiple tissues by quantitative PCR and in situ PCR of the GFP sequence. No teratoma was found in the tissues. Conclusions: Cynomolgus ES cells can be engrafted in the allogeneic fetus. We are now trying to transplant cynomolgus ES cells differentiated to neural or hematopoietic lineage.