Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects

被引：2

作者：

He, Ningning ^{[1
]}

Dong, Mingxin ^{[2
,3
]}

Sun, Yuxiao ^{[1
]}

Yang, Mengmeng ^{[1
]}

Wang, Yan ^{[1
]}

Du, Liqing ^{[1
]}

Ji, Kaihua ^{[1
]}

Wang, Jinhan ^{[1
]}

Zhang, Manman ^{[1
]}

Gu, Yeqing ^{[1
]}

Lu, Xinran ^{[1
]}

Liu, Yang ^{[1
]}

Wang, Qin ^{[1
]}

Li, Zongjin ^{[4
]}

Song, Huijuan ^{[1
]}

Xu, Chang ^{[1
]}

Liu, Qiang ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Radiat Med, State Key Lab Adv Med Mat & Devices, Tianjin Key Lab Radiat Med & Mol Nucl Med, Tianjin 300192, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Expt Hematol, Inst Hematol, Natl Clin Res Ctr Blood Dis,Haihe Lab Cell Ecosyst, Tianjin 300020, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Blood Dis Hosp, Tianjin 300020, Peoples R China

[4] Nankai Univ, Sch Med, Tianjin, Peoples R China

来源：

THERANOSTICS | 2024年 / 14卷 / 14期

基金：

中国国家自然科学基金;

关键词：

extracellular vesicles; mesenchymal stem cells; nanotherapeutics; radiation; intestinal injury; EXPERIMENTAL COLITIS; RADIATION-INJURY; EXOSOMES; STAT3; TRANSPLANTATION; INFLAMMATION; EXPRESSION; PROTECT; REPAIR;

D O I：

10.7150/thno.97623

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Radiation-induced intestinal injuries are common in patients with pelvic or abdominal cancer. However, these injuries are currently not managed effectively. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been extensively used in regenerative medicine. However, the results of MSC-EVs in the repair of radiation-induced intestinal damage have been unsatisfactory. We here investigated the nanotherapeutic functions of MSC-EVs in radiation-induced intestinal injury. Methods: We visualized the biodistribution and trend of MSC-EVs through in vivo imaging. A radiationinduced intestinal injury model was constructed, and the therapeutic effect of MSC-EVs was explored through in vivo and in vitro experiments. Immunofluorescence and qRT-PCR assays were conducted to explore the underlying mechanisms. Results: MSC-EVs exhibited a dose-dependent tendency to target radiation-injured intestines while providing spatiotemporal information for the early diagnosis of the injury by quantifying the amount of MSC-EVs in the injured intestines through molecular imaging. Meanwhile, MSC-EVs displayed superior nanotherapeutic functions by alleviating apoptosis, improving angiogenesis, and ameliorating the intestinal inflammatory environment. Moreover, MSC-EVs-derived miRNA-455-5p negatively regulated SOCS3 expression, and the activated downstream Stat3 signaling pathway was involved in the therapeutic efficacy of MSC-EVs in radiation-induced intestinal injuries. Conclusion: MSC-EVs can dose-dependently target radiation-injured intestinal tissues, allow a spatiotemporal diagnosis in different degrees of damage to help guide personalized therapy, offer data injury, and provide cell-free treatment for radiation therapy.

引用

页码：5492 / 5511

页数：20