Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.
OBJECTIVE
We have previously reported that bone marrow (BM)-derived cells contribute to the regeneration of the human intestinal epithelium. To analyze further how these cells arise, proliferate, and differentiate as epithelial cells, histologic analysis was conducted using endoscopic specimens.


METHODS
Thirty biopsy specimens from 14 female, sex-mismatched BM-transplantation recipients were examined. BM-derived cells were identified by fluorescent in situ hybridization (FISH) for the Y chromosome and immunohistochemistry. Multicolor FISH was used to exclude cell fusion. These cells were further analyzed for various differentiation or proliferation markers.


RESULTS
No evidence of cell fusion was detected. BM-derived cells did not distribute within the crypt as stem cells and rarely expressed Musashi-1. However, BM-derived epithelial cells frequently expressed Ki-67, and some of these cells appeared as pairs of adjacent cells. These cells also expressed markers of all 4 lineages of terminally differentiated cells. During regeneration following graft-vs-host disease, the number of BM-derived cells was substantially increased within Ki-67-positive cells. Interestingly, the number of cells expressing markers for secretory lineage cells was significantly increased within BM-derived cells. This change was unique for BM-derived cells, resulting in a significantly increased proportion of BM-derived cells among secretory lineage cells.


CONCLUSIONS
BM-derived epithelial cells arise via a mechanism other than cell fusion and rarely give rise to stem cells. However, a small proportion of these cells express proliferation markers, and a majority reside as terminally differentiated cells. During regeneration BM-derived cells increase as secretory lineage cells, thereby contributing to restore epithelial functions.
Matsumoto
Tomoko
T
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan.
Okamoto
Ryuichi
R
Yajima
Tomoharu
T
Mori
Takehiko
T
Okamoto
Shinichiro
S
Ikeda
Yasuo
Y
Mukai
Makio
M
Yamazaki
Motomi
M
Oshima
Shigeru
S
Tsuchiya
Kiichiro
K
Nakamura
Tetsuya
T
Kanai
Takanori
T
Okano
Hideyuki
H
Inazawa
Johji
J
Hibi
Toshifumi
T
Watanabe
Mamoru
M
D001706:Biopsy; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002459:Cell Fusion; D049109:Cell Proliferation; D041322:Chromosomes, Human, Y; D004064:Digestive System / Q000166:cytology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D012038:Regeneration; D013234:Stem Cells