CDK1-loaded extracellular vesicles promote cell cycle to reverse impaired wound healing in diabetic obese mice

被引：0

作者：

Choi, Wooil ^{[1
]}

Park, Dong Jun ^{[1
]}

Dorschner, Robert A. ^{[2
]}

Nakatsutsumi, Keita ^{[1
]}

Yi, Michelle ^{[1
]}

Eliceiri, Brian P. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Dept Surg, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Dermatol, La Jolla, CA 92093 USA

来源：

MOLECULAR THERAPY | 2025年 / 33卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HISTONE H3; PHOSPHORYLATION; CDK1; 4E-BP1; PATHWAY; KINASE; ACTIVATION; EXOSOMES; PROLIFERATION; INFLAMMATION;

D O I：

10.1016/j.ymthe.2025.01.039

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Small extracellular vesicles (sEVs) mediate intercellular signaling to coordinate the proliferation of cell types that promote re-epithelialization of skin following injury. Cyclindependent kinase 1 (CDK1) drives cell division and is a key regulator of entry to the cell cycle. To understand the potential of sEV-mediated delivery of CDK1 to reverse impaired wound healing, we generated CDK1-loaded sEVs (CDK1-sEVs) and evaluated their ability to mediate cell proliferation, re-epithelialization, and downstream signaling responses in the wound bed. We found that treatment of human keratinocytes with CDK1-sEVs increased phosphorylation of the CDK1 target, eukaryotic translation inhibition factor 4E-binding protein 1 (4E-BP1), and histone H3 within 24 h via AKT and ERK phosphorylation, driving increased proliferation and cell migration. Treatment of the wound bed of diabetic obese mice, a model of delayed wound healing, with a single dose of CDK1-sEVs accelerated wound closure, increased re-epithelialization, and promoted the proliferation of keratinocytes. These studies show that delivery of CDK1 by sEVs can stimulate selective and transient proliferation of cell types that increase re-epithelialization and promote proliferation of keratinocytes to accelerate wound healing.

引用

页码：1118 / 1133

页数：16