Extracellular vesicles derived from human placental mesenchymal stem cells alleviate experimental colitis in mice by inhibiting inflammation and oxidative stress

Duan,Liyun; Huang,Haoyan; Zhao,Xiaotong; Zhou,Manqian; Chen,Shang; Wang,Chen; Han,Zhibo; Han,Zhong-Chao; Guo,Zhikun; Li,Zongjin; Cao,Xiaocang

doi:10.3892/ijmm.2020.4679

Extracellular vesicles derived from human placental mesenchymal stem cells alleviate experimental colitis in mice by inhibiting inflammation and oxidative stress

Authors:
- Liyun Duan
- Haoyan Huang
- Xiaotong Zhao
- Manqian Zhou
- Shang Chen
- Chen Wang
- Zhibo Han
- Zhong-Chao Han
- Zhikun Guo
- Zongjin Li
- Xiaocang Cao
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Affiliations: Department of Hepato-Gastroenterology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300071, P.R. China, School of Medicine, Nankai University, Tianjin 300071, P.R. China, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Radiation Oncology, Tianjin Union Medical Center, Tianjin 300121, P.R. China, Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health and Biotech Co., Beijing 100176, P.R. China
Published online on: July 17, 2020 https://doi.org/10.3892/ijmm.2020.4679
Pages: 1551-1561
Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mesenchymal stem cells (MSCs) are pluripotent cells that can be applied to the treatment of immune disorders, including inflammatory bowel disease (IBD). The therapeutic effects of MSCs have been mostly attributed to the secretion of soluble factors with paracrine actions, such as extracellular vesicles (EVs), which may play a relevant role in the repair of damaged tissues. In the present study, a mouse model of colitis was induced with the use of trinitrobenzene sulfonic acid (TNBS). EVs derived from human placental mesenchymal stem cells (hP‑MSCs) were used for the treatment of colitis by in situ injection. Clinical scores were applied to verify the therapeutic effects of EVs on mice with colitis. Inflammation in the colon was evaluated by measuring the levels of various inflammatory cytokines. The content of reactive oxygen species (ROS) was detected by the use of molecular imaging methods for real‑time tracking and the therapeutic effects of EVs on mucosal healing in mice with colitis were evaluated. The results revealed that the injection of EVs regulated the balance of pro‑inflammatory and anti‑inflammatory cytokines in colon tissue. Treatment with EVs also suppressed oxidative stress by decreasing the activity of myeloperoxidase (MPO) and ROS. Histological analysis further confirmed that the EVs significantly promoted mucosal healing, as reﬂected by the promotion of the proliferation of colonic epithelial cells and the maintenance of tight junctions. Taken together, the findings of the present study demonstrated that EVs derived from hP‑MSCs alleviated TNBS‑induced colitis by inhibiting inflammation and oxidative stress. These findings may provide a novel theoretical basis for the EV‑based treatment of IBD.

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