Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal epithelial cells.
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.
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan. f_ishika@intmed1.med.kyushu-u.ac.jp
Fumihiko
F
Ishikawa
Masaki
M
Yasukawa
Shuro
S
Yoshida
Kei-Ichiro
K
Nakamura
Yoshihisa
Y
Nagatoshi
Takaaki
T
Kanemaru
Kazuya
K
Shimoda
Shinji
S
Shimoda
Toshihiro
T
Miyamoto
Jun
J
Okamura
Leonard D
LD
Shultz
Mine
M
Harada
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013234:Stem Cells / Q000737:chemistry
D018952:Antigens, CD34