Enhanced adipose-derived stem cells with IGF-1-modified mRNA promote wound healing following corneal injury

Fei Yu; Danni Gong; Dan Yan; Huijing Wang; Nevin Witman; Yang Lu; Wei Fu; Yao Fu

doi:10.1016/j.ymthe.2023.05.002

Enhanced adipose-derived stem cells with IGF-1-modified mRNA promote wound healing following corneal injury

Mol Ther. 2023 Aug 2;31(8):2454-2471. doi: 10.1016/j.ymthe.2023.05.002. Epub 2023 May 10.

Authors

Fei Yu¹, Danni Gong¹, Dan Yan¹, Huijing Wang², Nevin Witman³, Yang Lu⁴, Wei Fu⁵, Yao Fu⁶

Affiliations

¹ Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China.
² Institute of Pediatric Translational Medicine, Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
³ Department of Clinical Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
⁴ Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China. Electronic address: luyang8311@hotmail.com.
⁵ Institute of Pediatric Translational Medicine, Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: fuweizhulu@163.com.
⁶ Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China. Electronic address: drfuyao@126.com.

PMID: 37165618
PMCID: PMC10422019 (available on 2024-08-02)
DOI: 10.1016/j.ymthe.2023.05.002

Abstract

The cornea serves as an important barrier structure to the eyeball and is vulnerable to injuries, which may lead to scarring and blindness if not treated promptly. To explore an effective treatment that could achieve multi-dimensional repair of the injured cornea, the study herein innovatively combined modified mRNA (modRNA) technologies with adipose-derived mesenchymal stem cells (ADSCs) therapy, and applied IGF-1 modRNA (modIGF1)-engineered ADSCs (ADSC^modIGF1) to alkali-burned corneas in mice. The therapeutic results showed that ADSC^modIGF1 treatment could achieve the most extensive recovery of corneal morphology and function when compared not only with simple ADSCs but also IGF-1 protein eyedrops, which was reflected by the healing of corneal epithelium and limbus, the inhibition of corneal stromal fibrosis, angiogenesis and lymphangiogenesis, and also the repair of corneal nerves. In vitro experiments further proved that ADSC^modIGF1 could more significantly promote the activity of trigeminal ganglion cells and maintain the stemness of limbal stem cells than simple ADSCs, which were also essential for reconstructing corneal homeostasis. Through a combinatorial treatment regimen of cell-based therapy with mRNA technology, this study highlighted comprehensive repair in the damaged cornea and showed the outstanding application prospect in the treatment of corneal injury.

Keywords: IGF1-modified mRNA; adipose-derived mesenchymal stem cells; corneal alkali burn; corneal neovascularization; corneal nerves; corneal wound healing; limbal stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Animals
Cornea
Corneal Diseases*
Corneal Injuries* / genetics
Corneal Injuries* / metabolism
Corneal Injuries* / therapy
Insulin-Like Growth Factor I / genetics
Insulin-Like Growth Factor I / pharmacology
Mesenchymal Stem Cells* / metabolism
Mice
Wound Healing / genetics

Substances

Insulin-Like Growth Factor I