3,3'-Diindolylmethane stimulates exosomal Wnt11 autocrine signaling in human umbilical cord mesenchymal stem cells to enhance wound healing

Theranostics
Hui ShiWenrong Xu

Abstract

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 μM of DIM exhibited desirable repairing effects compared with untreated hucMSCs. DIM enhanced the stemness of hucMSCs, which was related to the activation of Wnt/β-catenin signaling. β-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 β-catenin activation and stemness induction in DIM-hucMSCs and abrogated their therapeutic effectsin 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.

Citations

Sep 27, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Mengdie LiYijie Shi
Aug 6, 2020·Journal of Inflammation Research·Zhixiao YaoCunyi Fan
Mar 23, 2018·Frontiers in Cardiovascular Medicine·Julia Christina Gross, Laura Cecilia Zelarayán
Jun 15, 2019·International Journal of Molecular Sciences·Elisa CarrascoMaría Mittelbrunn
Feb 23, 2020·Stem Cells International·Deyun ChenXiaobing Fu
Feb 1, 2020·Biomicrofluidics·Zhijie MaHaiyan Li
Nov 22, 2020·Burns : Journal of the International Society for Burn Injuries·Filip RangatchewRikke Holmgaard
Mar 16, 2021·Frontiers in Pharmacology·Wumei WeiXiaohong Tian
Apr 20, 2021·Advanced Drug Delivery Reviews·Anika NagelkerkeMolly M Stevens
Aug 7, 2021·Advanced Drug Delivery Reviews·Peiwen FuZhimin Tao
Sep 3, 2021·Stem Cells International·Can JinHui Qian
Sep 28, 2021·Frontiers in Cell and Developmental Biology·Chenyang GuLukui Chen

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Methods Mentioned

BETA
electrophoresis
light microscopy
transfection
protein assay
transmission electron microscopy
nuclear translocation
ELISA

Software Mentioned

Prism
NIH Image

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