title: Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat.
abstract: BACKGROUND
  Although mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, uncertainty remains concerning the distribution, function, and fate of repopulating MSCs in recipient colonic tissues. Therefore, we investigated the role of transplanted MSCs in the repair phase of DSS colitis.
  
  
  METHODS
  LacZ-labeled rat MSCs were transplanted into rats with colitis induced by 4% DSS on day 2. Regular water replaced the DSS solution on day 6. Therapeutic effect was evaluated on day 9 by clinicopathologic and growth factor/cytokine expression profiles. We analyzed the Notch signaling pathway by Western blotting and characterized immunofluorescence of lacZ-labeled MSCs with confocal laser microscopy. In vivo differentiation of MSC was confirmed by transmission electron microscopy (TEM).
  
  
  RESULTS
  Recovery of colitis was modestly but significantly promoted by MSC transplantation due to proceeding cell cycle and inhibiting apoptosis in the epithelia. Tgfa mRNA expression increased significantly, while Notch signaling was inhibited in the colonic tissues with MSC transplantation. β-Galactosidase-positive cells, which expressed α-SMA, desmin, and vimentin, were infrequently detected in the lamina propria stroma. DSS exposure in vitro proved to be the most potent inducer for α-SMA in MSCs where TEM demonstrated myogenic lineage differentiation.
  
  
  CONCLUSIONS
  We found that MSCs transplantation modestly promoted the repair of DSS colitis. The donor-derived MSCs were likely reprogrammed to differentiate to myogenic lineage cells by cues from the micro milieu. Further characterization of these cells is warranted as a basis for applying cell-based therapy for inflammatory bowel disease.
authors.affiliation: First Department of Internal Medicine, Sapporo Medical University, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Arimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yabana
authors.forename: Akira
authors.initials: A
authors.lastname: Goto
authors.forename: Masayo
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kanna
authors.initials: K
authors.lastname: Nagaishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Mineko
authors.initials: M
authors.lastname: Fujimiya
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000199:Actins; D016207:Cytokines; D003893:Desmin; D016264:Dextran Sulfate; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D014746:Vimentin; D001616:beta-Galactosidase; C498862:Acta2 protein, rat