PMID- 37256205
OWN - NLM
STAT- MEDLINE
DCOM- 20230602
LR  - 20230602
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 18
DP  - 2023
TI  - HucMSC-Exo Promote Mucosal Healing in Experimental Colitis by Accelerating 
      Intestinal Stem Cells and Epithelium Regeneration via Wnt Signaling Pathway.
PG  - 2799-2818
LID - 10.2147/IJN.S402179 [doi]
AB  - BACKGROUND: Mucosal healing has emerged as a crucial therapeutic goal for 
      inflammatory bowel diseases (IBD). Exosomes (Exo) as a potential acellular 
      candidate for stem cell therapy might be competent to promote mucosal healing, 
      while its mechanism remains unexplored. METHODS: Exosomes derived from human 
      umbilical cord mesenchymal stem cells (hucMSCs) were subjected to experimental 
      colitis mice intraperitoneally to estimate the role in mucosal healing and the 
      regeneration of intestinal stem cells (ISCs) and epithelium. The intestinal 
      organoid model of IBD was constructed utilizing tumor necrosis factor (TNF)-alpha for 
      subsequent function analysis in vitro. Transcriptome sequencing was performed to 
      decipher the underlying mechanism and Wnt-C59, an oral Wnt inhibitor, was used to 
      confirm that further. Finally, the potential specific components of hucMSC‑exo 
      were investigated based on several existing miRNA expression datasets. RESULTS: 
      HucMSC-exo showed striking potential for mucosal healing in colitis mice, 
      characterized by decreased histopathological injuries and neutrophil infiltration 
      as well as improved epithelial integrity. HucMSC-exo up-regulated the expression 
      of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a specific 
      marker for ISCs and accelerated the proliferation of intestinal epithelium. 
      HucMSC-exo endowed intestinal organoids with more excellent capacity to grow and 
      bud under TNF-alpha stimulation. More than that, the fact that hucMSC-exo activated 
      the canonical Wnt signaling pathway to promote mucosal healing was uncovered by 
      not only RNA-sequencing but also relevant experimental data. Finally, 
      bioinformatics analysis of the existing miRNA expression datasets indicated that 
      several miRNAs abundant in hucMSC-exo involved widely in regeneration or repair 
      related biological processes and Wnt signaling pathway might be one of the most 
      important signal transduction pathways. CONCLUSION: Our results suggested that 
      hucMSC-exo could facilitate mucosal healing in experimental colitis by 
      accelerating ISCs and intestinal epithelium regeneration via transferring key 
      miRNAs, which was dependent on the activation of Wnt/beta-catenin signaling pathway.
CI  - (c) 2023 Liang et al.
FAU - Liang, Xiaonan
AU  - Liang X
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Li, Chenyang
AU  - Li C
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Song, Jia
AU  - Song J
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Liu, Airu
AU  - Liu A
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Wang, Chen
AU  - Wang C
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Wang, Wenxin
AU  - Wang W
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Kang, Yaxing
AU  - Kang Y
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
AD  - Department of Endocrinology, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, People's Republic of China.
FAU - Sun, Donglei
AU  - Sun D
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
FAU - Qian, Jiaming
AU  - Qian J
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
AD  - Department of Gastroenterology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences and Peking Union Medical College, Beijing, People's 
      Republic of China.
FAU - Zhang, Xiaolan
AU  - Zhang X
AD  - Department of Gastroenterology, The Second Hospital of Hebei Medical University, 
      Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, 
      Hebei Clinical Research Center for Digestive Diseases, Shijiazhuang, Hebei, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20230525
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Wnt Signaling Pathway
MH  - *Exosomes/metabolism
MH  - Wound Healing/physiology
MH  - *Colitis/chemically induced/therapy/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - *Inflammatory Bowel Diseases
MH  - *Mesenchymal Stem Cells
MH  - Intestinal Mucosa/metabolism
MH  - Epithelium
MH  - Umbilical Cord
PMC - PMC10226545
OTO - NOTNLM
OT  - Wnt/beta-catenin signaling pathway
OT  - exosome
OT  - inflammatory bowel disease
OT  - mesenchymal stem cells
OT  - mucosal healing
COIS- The authors declare no potential conflicts of interest in this work.
EDAT- 2023/05/31 13:12
MHDA- 2023/06/02 06:43
PMCR- 2023/05/25
CRDT- 2023/05/31 10:38
PHST- 2023/01/31 00:00 [received]
PHST- 2023/05/19 00:00 [accepted]
PHST- 2023/06/02 06:43 [medline]
PHST- 2023/05/31 13:12 [pubmed]
PHST- 2023/05/31 10:38 [entrez]
PHST- 2023/05/25 00:00 [pmc-release]
AID - 402179 [pii]
AID - 10.2147/IJN.S402179 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2023 May 25;18:2799-2818. doi: 10.2147/IJN.S402179. 
      eCollection 2023.