Dataset Information

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

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 ?M of DIM exhibited desirable repairing effects compared with untreated hucMSCs. DIM enhanced the stemness of hucMSCs, which was related to the activation of Wnt/?-catenin signaling. ?-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 ?-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.

SUBMITTER: Shi H

PROVIDER: S-EPMC5436520 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Shi Hui H Xu Xiao X Zhang Bin B Xu Jiahao J Pan Zhaoji Z Gong Aihua A Zhang Xu X Li Rong R Sun Yaoxiang Y Yan Yongmin Y Mao Fei F Qian Hui H Xu Wenrong W

Theranostics 20170410 6

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 exhibit ...[more]

PMID: 28529644

Similar Datasets

Project description:: Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord-derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs. Through high-throughput RNA sequencing and functional analysis, we demonstrated that a group of uMSC-Exos enriched in specific microRNAs (miR-21, -23a, -125b, and -145) played key roles in suppressing myofibroblast formation by inhibiting the transforming growth factor-β2/SMAD2 pathway. Finally, using the strategy we established to block miRNAs inside the exosomes, we showed that these specific exosomal miRNAs were essential for the myofibroblast-suppressing and anti-scarring functions of uMSCs both in vitro and in vivo. Our study revealed a novel role of exosomal miRNAs in uMSC-mediated therapy, suggesting that the clinical application of uMSC-derived exosomes might represent a strategy to prevent scar formation during wound healing.SignificanceExosomes have been identified as a new type of major paracrine factor released by umbilical cord-derived mesenchymal stem cells (uMSCs). They have been reported to be an important mediator of cell-to-cell communication. However, it is still unclear precisely which molecule or group of molecules carried within MSC-derived exosomes can mediate myofibroblast functions, especially in the process of wound repair. The present study explored the functional roles of uMSC-exosomal microRNAs in the process of myofibroblast formation, which can cause excessive scarring. This is an unreported function of uMSC exosomes. Also, for the first time, the uMSC-exosomal microRNAs were examined by high-throughput sequencing, with a group of specific microRNAs (miR-21, miR-23a, miR-125b, and miR-145) found to play key roles in suppressing myofibroblast formation by inhibiting excess α-smooth muscle actin and collagen deposition associated with activity of the transforming growth factor-β/SMAD2 signaling pathway.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets