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Theranostics 2017; 7(6):1674-1688. doi:10.7150/thno.18082 This issue Cite

Research Paper

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

Hui Shi^1*, Xiao Xu^1*, Bin Zhang^1*, Jiahao Xu¹, Zhaoji Pan¹, Aihua Gong¹, Xu Zhang¹, Rong Li¹, Yaoxiang Sun¹, Yongmin Yan¹, Fei Mao¹, Hui Qian^1✉, Wenrong Xu^1*✉

1. Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China;
2. The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
* These authors have contributed equally to this work.

✉ Corresponding authors: Wenrong Xu, PhD, MD, Professor, School of Medicine, Jiangsu University, 301 Xuefu Road, Jiangsu 212013, China Tel: +86 511 85038215 Fax: +86 511 85038483 E-mail: iclsedu.cn; Hui Qian, PhD, Professor, School of Medicine, Jiangsu University, 301 Xuefu Road, Jiangsu 212013, China Tel: +86 511 85038334 Fax: +8651185038483 E-mail: lstmmmlstcom More

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 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.

Keywords: 3,3′-diindolylmethane, wound healing, Wnt11, exosome.

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