Novel nanopolymer RNA therapeutics normalize human diabetic corneal wound healing and epithelial stem cells
Diabetic cornea; Gene therapy; Limbal stem cells; Nanobioconjugate; RNA therapeutics; Wound healing; miRNA.- Nanomedicine
- 4.282
- 2021 Feb:32:102332.
- Mouse
- 流式
- 免疫/内分泌
- 干细胞
- 糖尿病
- CD115 (CSF-1R)
Abstract
Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met. NBC was internalized by LECs through transferrin receptor (TfR)-mediated endocytosis, inhibited cathepsin F or MMP-10 and upregulated c-Met. Non-toxic NBC modulating c-Met and cathepsin F accelerated wound healing in diabetic LECs and organ-cultured corneas vs. control NBC. NBC treatment normalized levels of stem cell markers (keratins 15 and 17, ABCG2, and ΔNp63), and signaling mediators (p-EGFR, p-Akt and p-p38). Non-toxic nano RNA therapeutics thus present a safe alternative to viral gene therapy for normalizing diabetic corneal cells.Keywords: Diabetic cornea; Gene therapy; Limbal stem cells; Nanobioconjugate; RNA therapeutics; Wound healing; miRNA.
金课堂之文献解析 文献原文请点击
本网站销售的所有产品及服务均不得用于人类或动物之临床诊断或治疗,仅可用于工业或者科研等非医疗目的。