Ishikawa Fumihiko, Yasukawa Masaki, Yoshida Shuro, Nakamura Kei-Ichiro, Nagatoshi Yoshihisa, Kanemaru Takaaki, Shimoda Kazuya, Shimoda Shinji, Miyamoto Toshihiro, Okamura Jun, Shultz Leonard D, Harada Mine
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
FASEB J. 2004 Dec;18(15):1958-60. doi: 10.1096/fj.04-2396fje. Epub 2004 Oct 5.
In the present study, we aimed to clarify the capacity of human cord blood- and bone marrow-derived progenitor cells to generate gastrointestinal epithelial cells in clinical and experimental transplantation settings. First, in a clinical transplantation setting, gastrointestinal tissues derived from female pediatric or juvenile recipients of allogeneic sex-mismatched bone marrow and cord blood transplantation were examined for the presence of donor-derived epithelial cells. Gastrointestinal specimens of allogeneic recipients included Y chromosome+ cytokeratin+ epithelial cells at a frequency of 0.4-1.9%. To further determine the capacity of purified human progenitor cells, human cord blood- or bone marrow-derived CD34+ cells were transplanted into newborn NOD/SCID/beta2-microglobulin(null) mice as an experimental transplantation assay. When gastrointestinal tissues derived from recipient mice were subjected to FISH and immunofluorescence analyses, human epithelial cells were identified at a frequency of 0.24-0.58% at 3 months posttransplantation. Finally, double FISH analyses using species-specific probes revealed that human chromosome+ epithelial cells did not possess any murine chromosomes, indicating that donor-derived epithelial cells were not generated only by cell fusion. On the basis of these findings, it is concluded that purified human cord blood and bone marrow CD34+ progenitor cells can generate gastrointestinal epithelial cells across allogeneic and xenogeneic histocompatibility barriers.
