Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model.

Autor: Koh AE; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia., Alsaeedi HA; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia., Rashid MBA; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Lam C; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Harun MHN; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Ng MH; Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia., Mohd Isa H; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Then KY; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Bastion MC; Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia., Farhana A; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia., Khursheed Alam M; Department of Orthodontics, College of Dentistry, Jouf University, Sakaka, Saudi Arabia., Subbiah SK; Department of Medical Microbiology, Universiti Putra Malaysia, Serdang, Malaysia.; Genetics and Regenerative Medicine Research Group, Universiti Putra Malaysia, Serdang, Malaysia.; Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, India., Mok PL; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.; Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia.; Genetics and Regenerative Medicine Research Group, Universiti Putra Malaysia, Serdang, Malaysia.; Centre for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, India.
Jazyk: angličtina
Zdroj: Frontiers in cell and developmental biology [Front Cell Dev Biol] 2021 Apr 27; Vol. 9, pp. 652017. Date of Electronic Publication: 2021 Apr 27 (Print Publication: 2021).
DOI: 10.3389/fcell.2021.652017
Abstrakt: Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSC EPO ) improved its regenerative capabilities in vitro . Hence, in this study, we sought to prove its potential in vivo by transplanting MSCs EPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCs EPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSC EPO -treated group had detectable ERG waves ( P <0.05), which were indicative of successful phototransduction. The stem cells were also successfully detected by immunohistochemistry 30 days after intravitreal transplantation. An initial over-representation analysis revealed a snapshot of immune-related pathways in all the groups but was mainly overexpressed in the MSC group. A subsequent GSEA and SPIA analysis later revealed enrichment in a large number of biological processes including phototransduction, regeneration, and cell death ( P adj <0.05). Based on these pathways, a set of pro-survival gene expressions were extracted and tabulated. This study provided an in-depth transcriptomic analysis on the MSC EPO -treated retinal degeneration model as well as a profile of pro-survival genes that can be used as candidates for further genetic enhancement studies on stem cells.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Koh, Alsaeedi, Rashid, Lam, Harun, Ng, Mohd Isa, Then, Bastion, Farhana, Khursheed Alam, Subbiah and Mok.)
Databáze: MEDLINE
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