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载有抗菌肽/LL-37 的工程化外泌体表现出多种生物学功能。

Engineered Exosomes Containing Cathelicidin/LL-37 Exhibit Multiple Biological Functions.

机构信息

Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, 97331, USA.

出版信息

Adv Healthc Mater. 2022 Oct;11(20):e2200849. doi: 10.1002/adhm.202200849. Epub 2022 Aug 12.

Abstract

Exosomes show great potential in diagnostic and therapeutic applications. Inspired by the human innate immune defense, herein, we report engineered exosomes derived from monocytic cells treated with immunomodulating compounds 1α,25-dihydroxyvitamin D 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 can be used as therapeutics alone or in combination with other biomaterials for effective infection management, wound healing, and tissue regeneration.

摘要

外泌体在诊断和治疗应用中具有巨大的潜力。受人体先天免疫防御机制的启发,我们在此报告了源自单核细胞的工程化外泌体,这些外泌体经免疫调节化合物 1α,25-二羟维生素 D 和 CYP24A1 抑制剂 VID400 处理,并从电纺纳米纤维基质中缓慢释放。与未经处理的细胞或 Cathelicidin Human Tagged ORF Clone 转染细胞衍生的外泌体相比,这些工程化外泌体含有明显更多的抗菌肽/LL-37。此外,这些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,或与其他生物材料联合使用,以有效进行感染管理、伤口愈合和组织再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f03f/11469144/b37511ce5a34/ADHM-11-2200849-g005.jpg

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