Efficiency of bone marrow-derived cells in regeneration of the stomach after induction of ethanol-induced ulcers in rats.
BACKGROUND
Bone marrow contains hematopoietic stem cells, nonhematopoietic mesenchymal stem cells, and several precursor cells for osteoblasts, chondrocytes, adipocytes, myocytes, hepatocytes, and even neural cells. Research findings indicate that multipotent stem cells in the adult body may be used to recover the lost functions of damaged tissues. This study examined the involvement of bone marrow-derived cells in the regeneration of the stomach after experimental gastric ulcers were produced in rats.


METHODS
We transplanted the bone marrow of transgenic rats that expressed green fluorescence protein (GFP) throughout the body. Twenty-one days after the bone marrow transplantation (BMT), gastric ulceration was induced, using absolute ethanol. Control animals received saline. After various observation periods, rats harboring GFP-positive bone marrow-derived cells were killed, and the tissues were removed and processed to prepare paraffin-embedded sections. Cells expressing GFP were identified by conventional immunohistochemistry, using anti-GFP antibody. To identify whether cells expressing GFP were epithelial cells or interstitial cells such as fibroblasts, serial sections were examined with anti-cytokeratin antibody or anti-vimentin antibody, respectively. Furthermore, to confirm that cells expressing GFP were epithelial cells or interstitial cells, we used double-staining analysis with anti-GFP antibody or anti-cytokeratin antibody, respectively.


RESULTS
GFP-positive, bone marrow-derived cells were found in the cytokeratin-positive gastrointestinal epithelium, as well as among vimentin-positive interstitial cells. Interestingly, the proportions of GFP-positive, cytokeratin-positive epithelial cells and vimentin-positive interstitial cells were significantly greater in the ethanol-treated damaged stomachs than in the saline-treated controls.


CONCLUSIONS
The present study clearly demonstrates that bone marrow-derived cells are involved in the regeneration of the stomach after ethanol-induced ulcers in rats.
Komori
Masato
M
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan.
Tsuji
Shingo
S
Tsujii
Masahiko
M
Murata
Hiroaki
H
Iijima
Hideki
H
Yasumaru
Masakazu
M
Nishida
Tsutomu
T
Irie
Takanobu
T
Kawano
Sunao
S
Hori
Masatsugu
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007633:Keratins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D012720:Severity of Illness Index; D013270:Stomach / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
D002492:Central Nervous System Depressants; D049452:Green Fluorescent Proteins; D000431:Ethanol; D007633:Keratins