Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-09-17

AUTHORS

Hiroki Tanaka, Yoshiaki Arimura, Takashi Yabana, Akira Goto, Masayo Hosokawa, Kanna Nagaishi, Kentaro Yamashita, Hiroyuki Yamamoto, Yasushi Sasaki, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura

ABSTRACT

BackgroundAlthough 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.MethodsLacZ-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).ResultsRecovery 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.ConclusionsWe 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. More... »

PAGES

143-152

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00535-010-0320-7

DOI

http://dx.doi.org/10.1007/s00535-010-0320-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021669494

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20848145


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34 schema:description BackgroundAlthough 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.MethodsLacZ-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).ResultsRecovery 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.ConclusionsWe 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.
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42 DSS
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44 DSS exposure
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46 MSC transplantation
47 Notch
48 Notch signaling
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50 Tgfa mRNA expression
51 Western blotting
52 apoptosis
53 basis
54 blotting
55 bowel disease
56 cell cycle
57 cell-based therapies
58 cells
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61 colitis
62 colonic tissue
63 confocal laser microscopy
64 cues
65 cycle
66 cytokine expression profile
67 day 2
68 day 6
69 day 9
70 desmin
71 dextran sulfate sodium-induced colitis
72 differentiation
73 disease
74 distribution
75 donor-derived mesenchymal stem cells
76 effect
77 electron microscopy
78 epithelium
79 evidence
80 exposure
81 expression
82 expression profiles
83 fate
84 function
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86 immunofluorescence
87 inducer
88 inflammatory bowel disease
89 intestinal tissue repair
90 lamina propria stroma
91 laser microscopy
92 lineage cells
93 lineage differentiation
94 lineages
95 mRNA expression
96 mesenchymal stem cells
97 microscopy
98 milieu
99 myogenic lineage
100 myogenic lineage differentiation
101 pathway
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105 rat mesenchymal stem cells
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108 regular water
109 repair
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111 role
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