Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

Ahead of print

doi: 10.17219/acem/156643

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Sang H, Zhao R, Lai G, et al. Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic transplantation [published online as ahead of print on March 7, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/156643

Bone marrow mesenchymal stem cell-derived exosomes attenuate the maturation of dendritic cells and reduce the rejection of allogeneic transplantation

Hongxun Sang1,A, Renli Zhao2,B, Guohua Lai2,3,B,C, Zhiwei Deng4,B,C, Weida Zhuang1,C,E, Mingjie Wu3,C,E, Jiachang Wu1,A,E

1 Department of Orthopedic Surgery, Shenzhen Hospital of Southern Medical University, China

2 The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China

4 Division of Spine Surgery, Section II, Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Southern Medical University, Academy of Orthopedics of Guangdong Province, Guangzhou, China


Background. Bone mesenchymal stem cell (BMSC)-derived exosomes (B-exos) are attractive for applications in enabling alloantigen tolerance. An in-depth mechanistic understanding of the interaction between B-exos and dendritic cells (DCs) could lead to novel cell-based therapies for allogeneic transplantation.
Objectives. To examine whether B-exos exert immunomodulatory effects on DC function and maturation.
Material and Methods. After mixed culture of BMSCs and DCs for 48 h, DCs from the upper layer were collected to analyze the expression levels of surface markers and mRNAs of inflammation-related cytokines. Then, before being collected to detect the mRNA and protein expression levels of indoleamine 2,3-dioxygenase (IDO), the DCs were co-cultured with B-exos. Then, the treated DCs from different groups were co-cultured with naïve CD4+ T cells from the mouse spleen. The proliferation of CD4+ T cells and the proportion of CD4+CD25+Foxp3+ T cells were analyzed. Finally, the skins of BALB/c mice were transplanted to the back of C57 mice in order to establish a mouse allogeneic skin transplantation model.
Results. The co-culture of DCs with BMSCs downregulated the expression of the major histocompatibility complex class II (MHC-II) and CD80/86 costimulatory molecules on DCs. Moreover, B-exos increased the expression of IDO in DCs treated with lipopolysaccharide (LPS). The proliferation of CD4+CD25+Foxp3+ T cells increased when cultured with B-exos-exposed DCs. Finally, mice recipients injected with B-exos-treated DCs had significantly prolonged survival after receiving the skin allograft.
Conclusion. Taken together, these data suggest that the B-exos suppress the maturation of DCs and increase the expression of IDO, which might shed light on the role of B-exos in inducing alloantigen tolerance.

Key words

exosomes, tolerance, bone marrow mesenchymal stem cell

Graphical abstract

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