Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions.
Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions.
复制标题
载有抗菌肽/LL - 37的工程化外泌体展现出多种生物学功能。
DOI：
10.1002/adhm.202200849
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发表时间：
2022-10
影响因子：
10
通讯作者：
Xie, Jingwei
中科院分区：
文献类型：
--
作者：
Su, Yajuan;Sharma, Navatha Shree;John, Johnson V.;Ganguli-Indra, Gitali;Indra, Arup K.;Gombart, Adrian F.;Xie, Jingwei
关键词：
外泌体在诊断和治疗应用中显示出巨大的潜力。受人类先天性免疫防御的启发，本文中，我们报告了用免疫调节化合物1α，25-二羟基维生素D3和CYP 24 A1抑制剂VID 400处理的单核细胞衍生的工程化外泌体，其从电纺基质中缓慢释放。与来源于未处理细胞或Cathelicidin人标记ORF克隆转染细胞的外泌体相比，这些工程化外泌体含有显著更多的Cathelicidin/LL-37。此外，此类外泌体还表现出多种生物学功能，包括杀死细菌、促进人脐静脉内皮细胞管形成以及增强皮肤细胞增殖和迁移。总之，本研究中开发的工程化外泌体可单独用作治疗剂或与其他生物材料组合用于有效的感染管理，伤口愈合和组织再生。当与来源于未处理的细胞或Cathelicidin人标记ORF克隆转染的细胞的外泌体相比时，来源于单核细胞的外泌体在用负载免疫调节化合物的电纺膜处理后含有显著更多的Cathelicidin/LL-37。这种外来体显示出几种生物学功能，其通过杀死细菌、促进人脐静脉内皮细胞管形成和增强皮肤细胞增殖和迁移来证明。
Exosomes show great potential in diagnostic and therapeutic applications. Inspired by human innate immune defense, herein, we report engineered exosomes-derived from monocytic cells treated with immunomodulating compounds 1α,25-dihydroxyvitamin D3 and CYP24A1 inhibitor VID400 which are slowly released from electrospun nanofiber matrices. These engineered exosomes contain significantly more cathelicidin/LL-37 when compared with exosomes-derived from either untreated cells or Cathelicidin Human Tagged ORF Clone transfected cells. In addition, such exosomes exhibit multiple biological functions evidenced by killing bacteria, facilitating human umbilical vein endothelial cell tube formation, and enhancing skin cell proliferation and migration. Taken together, the engineered exosomes developed in this study could be used as therapeutics alone or in combination with other biomaterials for effective infection management, wound healing, and tissue regeneration. Exosomes derived from monocytic cells after treatment with immunomodulating compounds-loaded electrospun nanofiber membranes contain significantly more cathelicidin/LL-37 when compared with exosomes derived from either untreated cells or Cathelicidin Human Tagged ORF Clone transfected cells. Such exosomes display several biological functions evidenced by killing bacteria, facilitating human umbilical vein endothelial cell tube formation, and enhancing skin cell proliferation and migration.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
4.9
作者：
Su, Yajuan;Ganguli-Indra, Gitali;Bhattacharya, Nilika;Logan, Isabelle E.;Indra, Arup K.;Gombart, Adrian F.;Wong, Shannon L.;Xie, Jingwei
通讯作者：
Xie, Jingwei
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
4.4
作者：
Samaeekia R;Rabiee B;Putra I;Shen X;Park YJ;Hematti P;Eslani M;Djalilian AR
通讯作者：
Djalilian AR
影响因子：
3.4
作者：
Mathivanan, Suresh;Simpson, Richard J.
通讯作者：
Simpson, Richard J.