Cultured bone marrow cell local implantation accelerates healing of ulcers in mice.
BACKGROUND
The therapeutic potential of bone marrow (BM)-derived cells in ulcers is not known. This study aimed to clarify (1) cell types that are derived from the BM which infiltrate ulcers; (2) whether BM-derived cells or gastric myofibroblasts can be used for cell transplantation to treat ulcers; and (3) the phenotypes of such transplantable cells.


METHODS
(1) Wild-type mice were transplanted with BM cells of green fluorescent protein (GFP)-transgenic mice. Acetic acid-induced gastric ulcers were produced in mice after BM transplantation. (2) BM cells and gastric myofibroblasts were isolated from GFP-transgenic mice. Bone marrow cells attached to plastic dishes were selected for expansion. Gastric ulcers were induced, and BM-derived cells, myofibroblasts, or phosphate-buffered saline were injected around ulcers. The ulcer healing process was examined macroscopically and histologically. (3) Expression of growth factors and cytokines in transplantable cells was examined by reverse transcriptase-polymerase chain reaction.


RESULTS
(1) GFP-positive cells with interstitial phenotypes were observed at the ulcerated area. (2) Ulcer healing was significantly promoted by the injection of BM-derived cells compared to controls on day 7, but not on day 3. The BM-derived cells were observed in the tissue surrounding the ulcer. However, myofibroblasts were not found. (3) The BM-derived cells expressed hepatocyte growth factor, transforming growth factor-beta(1), and other stromal factors before transplantation, and had mesenchymal phenotypes after transplantation.


CONCLUSIONS
BM-derived cells are involved in the ulcer healing. BM-derived cells, but not myofibroblasts, are locally implantable to ulcers. Thus, BM-derived cells can be transplanted to accelerate ulcer healing.
Nishida
Tsutomu
T
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Clinical Research Building (K1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Japan.
Tsuji
Shingo
S
Tsujii
Masahiko
M
Ishii
Shuji
S
Yoshio
Toshiyuki
T
Shinzaki
Shinichiro
S
Egawa
Satoshi
S
Irie
Takanobu
T
Kakiuchi
Yoshimi
Y
Yasumaru
Masakazu
M
Iijima
Hideki
H
Tsutsui
Shusaku
S
Kawano
Sunao
S
Hayashi
Norio
N
D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D016026:Bone Marrow Transplantation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery*; D014945:Wound Healing / Q000502:physiology*
D019342:Acetic Acid