Exosomes frombone marrow‑derived mesenchymal stem cells
facilitate corneal wound healing viaregulating thep44/42 MAPK
JinZhou1· YuanyuanDing2· YongqiangZhang3· DehuiZheng1· LifengYan1· MengxiangGuo1· YaniMao1·
Received: 21 June 2022 / Revised: 4 December 2022 / Accepted: 21 December 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem
cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-
activated protein kinase (MAPK) pathway.
Methods The isolated BMSC-Exos were identiﬁed by transmission electron microscopy, Western blot, and nanoparticle
tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs)
were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model
of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and
expression of α-SMA (a ﬁbrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected.
Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was
activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the eﬀects of BMSC-Exos on promoting the
proliferation and migration of HCEs. In vivo, the injection of BMSC-Exos facilitated the remission of the pathological changes (inﬂam-
mation) and weakened the upregulation of α-SMA (ﬁbrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury.
Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in
vitro and also inhibited alkali burn-induced inﬂammation, ﬁbrosis, and vascularization in corneal tissues in vivo. BMSC-
Exos may be promising resources for promoting corneal wound healing.
Keywords Bone marrow-derived mesenchymal stem cell· Exosome· Human corneal epithelial cell· Corneal wound healing
BMSC-Exos exhibit therapeutic potential in corneal diseases.
BMSC-Exos promote the proliferation and migration of HCEs.
BMSC-Exos activate the p44/42 MAPK pathway in HCEs.
BMSC-Exos facilitate corneal wound healing in mice.
Jin Zhou and Yuanyuan Ding contributed equally.
* Jin Zhou
1 Department ofOphthalmology, Guangzhou Women
andChildren’s Medical Center, No. 9, Jinsui Road, Tianhe
District, GuangzhouCity510623, China
2 Department ofOphthalmology, Nanfang Hospital, Southern
Medical University, GuangzhouCity510515, China
3 Department ofOphthalmology, Beijing Children’s Hospital
East Branch, BeijingCity100002, China
/ Published online: 28 December 2022
Graefe's Archive for Clinical and Experimental Ophthalmology (2023) 261:723–734