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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
Human cord blood- and bone marrow-derived CD34+ cells regenerate gastrointestinal epithelial cells
Fumihiko Ishikawa1, Masaki Yasukawa, Shuro Yoshida
1Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan. f_ishika@intmed1.med.kyushu-u.ac.jp
Insights
Human progenitor cells from cord blood and bone marrow can form gastrointestinal epithelial cells. This finding holds true in both clinical and experimental transplantation settings, offering new avenues for regenerative medicine.
Area of Science:
- Stem Cell Biology
- Gastroenterology
- Regenerative Medicine
Background:
- Human progenitor cells are crucial for tissue regeneration.
- The potential of cord blood and bone marrow progenitor cells to generate gastrointestinal epithelium is not fully understood.
- Understanding this capacity is vital for transplantation and regenerative therapies.
Purpose of the Study:
- To investigate the ability of human cord blood and bone marrow progenitor cells to differentiate into gastrointestinal epithelial cells.
- To assess this potential in both clinical and experimental transplantation models.
- To confirm the origin of these epithelial cells and rule out cell fusion as the sole mechanism.
Main Methods:
- Analysis of gastrointestinal tissues from human recipients of allogeneic transplants.
- Experimental transplantation of human CD34+ progenitor cells into immunodeficient mice.
- Fluorescence in situ hybridization (FISH) and immunofluorescence staining to detect donor-derived cells.
- Double FISH with species-specific probes to exclude cell fusion.
Main Results:
- Donor-derived Y chromosome+ epithelial cells were detected in human recipients (0.4-1.9%).
- Human epithelial cells were identified in mouse gastrointestinal tissues post-transplantation (0.24-0.58%).
- FISH analysis confirmed that human epithelial cells did not originate from cell fusion with mouse cells.
Conclusions:
- Human cord blood and bone marrow CD34+ progenitor cells possess the capacity to generate gastrointestinal epithelial cells.
- This differentiation occurs across allogeneic and xenogeneic histocompatibility barriers.
- These findings support the therapeutic potential of these progenitor cells for gastrointestinal repair.
Abstract:
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.
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