Bone marrow mesenchymal stem cells modified by angiogenin‐1 promotes tissue repair in mice with oxygen‐induced retinopathy of prematurity by promoting retinal stem cell proliferation and differentiation

Abstract

Retinopathy has become one of the major factors that lead to blindness worldwide.Although many clinical therapies are concerned about such disease, most of them focus on symptoms alleviation. In this study, we aim to investigate whether coculture retinal stem cells (RSCs) with bone marrow mesenchymal stem cells transfected with angiogenin-1 (Ang-1-BMSCs) affects the damaged retinal tissue of oxygen-induced retinopathy of prematurity (OIR-ROP) mice. After OIR-ROP mouse model establishment, Ang-1-BMSCs, RSCs, and OIR-ROP retinal tissues were cocultured in a a transwell chamber. RSCs proliferation and the expression of Ang-1, insulin-like growth factor-1 (IGF-1) in the supernatant of RSCs, as well as β-tubulin and protein kinase C (PKC) expression were evaluated. Finally, the repair of OIR-ROP mice retinal tissues was observed by injecting Ang-1-BMSCs + RSCs. In the OIR-ROP mouse model, RSCs cocultured with OIR-ROP retinal tissues could be induced to differentiate into cells expressing β-tubulin and PKC and promote the expression of Ang-1 and IGF-1. coculture of Ang-1-BMSCs further enhanced the proliferation and differentiation of RSCs by promoting the expression of Ang-1 and IGF-1. Coculture of RSCs + Ang-1-BMSCs induced differentiation of Ang-1-BMSCs through interaction among intercellular factors and restored the damaged retinal tissue of OIR-ROP mice. Collectively, our study provided evidence that coculture of Ang-1-BMSCs and RSCs could promote the proliferation and differentiation of RSCs and improve the treatment for the damaged retina tissue of OIR-ROP mice. K E Y W O R D S angiogenin-1, bone mesenchymal stem cells, coculture, differentiation, oxygen-induced retinopathy, proliferation, retinal stem cells, retinopathy of prematurity

Blood protein profiles related to preterm birth and retinopathy of prematurity

“…Interestingly, many of the identified proteins are related to both development and degeneration, representing impaired function at both ends of the lifespan. This is illustrated by the association of APP to both neurogenesis and neurodegenerative diseases as well as the correlation of ANGPT1 with both ROP and diabetic retinopathy 58 , 64 , 114 , 116 , 124 – 126 . Further on, there is a clear association between osteogenesis and bone metabolism, a mechanism one can believe is connected to hematopoiesis.…”

“…Nonetheless, some of the proteins have been acknowledged for the possible involvement in diabetic retinopathy or ROP: AGER, ANGPT1, CD40LG, GDF2, MMP12, SERPINE1, THBD, DKK1, PDGFA, and IL-18. 47 , 50 , 51 , 54 , 56 , 58 , 92 , 101 , 114 – 123 For example, Lamine et al 115 presented recently that CD40LG is associated to both occurrence and severity of type 2 diabetic retinopathy, which shares some physiological connections with ROP. Interestingly, many of the identified proteins are related to both development and degeneration, representing impaired function at both ends of the lifespan.…”

Progress in Research on Stem Cells in Neonatal Refractory Diseases

“…Retinal SCs (RSCs) can migrate, differentiate, and integrate into the retina ( Figure 16 ) [ 164 ]. The co-culture of BM-MSCs and RSCs transfected with Angular-1 can induce the differentiation of RSCs into β-tubulin and PKC, promote the expression of Ang-1 and IGF-1 and proliferation and differentiation of RSCs, and effectively improve the therapeutic effect of OIR-ROP in rats with retinal injury [ 165 ]. Other studies have suggested that BM-MSCs transfected with Ang-1 could improve the morphology of the injured optic nerve and repair the myelin sheath of nerve fibers, demonstrating its preventive and therapeutic effects on optic nerve injury in OIR rats [ 166 ].…”

Vascular and Neuronal Protection in the Developing Retina: Potential Therapeutic Targets for Retinopathy of Prematurity

“…Injected eyes displayed a significantly reduced avascular area and prevention of neovascularization. Other than eEPC and OEC, the effect of mesenchymal stem cells (MSCs) and adipose-derived stem cells (ASCs) were reported recently using the mouse OIR model [232,233,234,235]. MSCs or ASCs were injected into the OIR-treated mice at P12 intravitreally.…”