PMID- 28529644
OWN - NLM
STAT- MEDLINE
DCOM- 20180212
LR  - 20181202
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 7
IP  - 6
DP  - 2017
TI  - 3,3'-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human 
      umbilical cord mesenchymal stem cells to enhance wound healing.
PG  - 1674-1688
LID - 10.7150/thno.18082 [doi]
AB  - Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are suggested as a 
      promising therapeutic tool in regenerative medicine, however, their efficacy 
      requires improvement. Small molecules and drugs come up to be a convenient 
      strategy in regulating stem cells fate and function. Here, we evaluated 
      3,3'-diindolylmethane (DIM), a natural small-molecule compound involved in the 
      repairing effects of hucMSCs on a deep second-degree burn injury rat model. 
      HucMSCs primed with 50 muM of DIM exhibited desirable repairing effects compared 
      with untreated hucMSCs. DIM enhanced the stemness of hucMSCs, which was related 
      to the activation of Wnt/beta-catenin signaling. beta-catenin inhibition impaired the 
      healing effects of DIM-primed hucMSCs (DIM-hucMSCs) in vivo. Moreover, we 
      demonstrated that DIM upregulated Wnt11 expression in hucMSC-derived exosomes. 
      Wnt11 knockdown inhibited beta-catenin activation and stemness induction in 
      DIM-hucMSCs and abrogated their therapeutic effects in vivo. Thus, our findings 
      indicate that DIM promotes the stemness of hucMSCs through increased exosomal 
      Wnt11 autocrine signaling, which provides a novel strategy for improving the 
      therapeutic effects of hucMSCs on wound healing.
FAU - Shi, Hui
AU  - Shi H
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Xu, Xiao
AU  - Xu X
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Xu, Jiahao
AU  - Xu J
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Pan, Zhaoji
AU  - Pan Z
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Gong, Aihua
AU  - Gong A
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Li, Rong
AU  - Li R
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Sun, Yaoxiang
AU  - Sun Y
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Yan, Yongmin
AU  - Yan Y
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Mao, Fei
AU  - Mao F
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Qian, Hui
AU  - Qian H
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
FAU - Xu, Wenrong
AU  - Xu W
AD  - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of 
      Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
LA  - eng
PT  - Journal Article
DEP - 20170410
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Indoles)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt11 protein, human)
RN  - SSZ9HQT61Z (3,3'-diindolylmethane)
SB  - IM
MH  - Animals
MH  - Burns/pathology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Humans
MH  - Indoles/*metabolism
MH  - Mesenchymal Stem Cells/*drug effects/*physiology
MH  - Rats
MH  - *Signal Transduction
MH  - *Umbilical Cord
MH  - Wnt Proteins/*metabolism
MH  - *Wound Healing
PMC - PMC5436520
OTO - NOTNLM
OT  - 3,3'-diindolylmethane
OT  - Wnt11
OT  - exosome.
OT  - wound healing
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2017/05/23 06:00
MHDA- 2018/02/13 06:00
PMCR- 2017/01/01
CRDT- 2017/05/23 06:00
PHST- 2016/10/26 00:00 [received]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/05/23 06:00 [entrez]
PHST- 2017/05/23 06:00 [pubmed]
PHST- 2018/02/13 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - thnov07p1674 [pii]
AID - 10.7150/thno.18082 [doi]
PST - epublish
SO  - Theranostics. 2017 Apr 10;7(6):1674-1688. doi: 10.7150/thno.18082. eCollection 
      2017.