Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model
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...
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| Format: | Article |
| Language: | English |
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Frontiers
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/93428/ http://psasir.upm.edu.my/id/eprint/93428/1/Transplanted%20erythropoietin-expressing.pdf |
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| author | Koh, Avin Ee Hwan Alsaeedi, Hiba Amer Abd Rashid, Munirah Lam, Chenshen Harun, Mohd Hairul Nizam Ng, Min Hwei Mohd Isa, Hazlita Then, Kong Yong Mae-Lynn, Catherine Bastion Aisha Farhana Alam, Mohammad Khursheed Subbiah, Suresh Kumar Mok, Pooi Ling |
| author_facet | Koh, Avin Ee Hwan Alsaeedi, Hiba Amer Abd Rashid, Munirah Lam, Chenshen Harun, Mohd Hairul Nizam Ng, Min Hwei Mohd Isa, Hazlita Then, Kong Yong Mae-Lynn, Catherine Bastion Aisha Farhana Alam, Mohammad Khursheed Subbiah, Suresh Kumar Mok, Pooi Ling |
| author_sort | Koh, Avin Ee Hwan |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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 (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO 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 MSCEPO-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 (Padj <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 MSCEPO-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. |
| first_indexed | 2025-11-15T13:07:34Z |
| format | Article |
| id | upm-93428 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T13:07:34Z |
| publishDate | 2021 |
| publisher | Frontiers |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-934282022-11-22T08:53:15Z http://psasir.upm.edu.my/id/eprint/93428/ Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model Koh, Avin Ee Hwan Alsaeedi, Hiba Amer Abd Rashid, Munirah Lam, Chenshen Harun, Mohd Hairul Nizam Ng, Min Hwei Mohd Isa, Hazlita Then, Kong Yong Mae-Lynn, Catherine Bastion Aisha Farhana Alam, Mohammad Khursheed Subbiah, Suresh Kumar Mok, Pooi Ling 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 (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO 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 MSCEPO-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 (Padj <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 MSCEPO-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. Frontiers 2021-09 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/93428/1/Transplanted%20erythropoietin-expressing.pdf Koh, Avin Ee Hwan and Alsaeedi, Hiba Amer and Abd Rashid, Munirah and Lam, Chenshen and Harun, Mohd Hairul Nizam and Ng, Min Hwei and Mohd Isa, Hazlita and Then, Kong Yong and Mae-Lynn, Catherine Bastion and Aisha Farhana and Alam, Mohammad Khursheed and Subbiah, Suresh Kumar and Mok, Pooi Ling (2021) Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model. Frontiers in Cell and Developmental Biology, 9. pp. 1-27. ISSN 2296-634X https://www.frontiersin.org/articles/10.3389/fcell.2021.764504/full |
| spellingShingle | Koh, Avin Ee Hwan Alsaeedi, Hiba Amer Abd Rashid, Munirah Lam, Chenshen Harun, Mohd Hairul Nizam Ng, Min Hwei Mohd Isa, Hazlita Then, Kong Yong Mae-Lynn, Catherine Bastion Aisha Farhana Alam, Mohammad Khursheed Subbiah, Suresh Kumar Mok, Pooi Ling Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title | Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title_full | Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title_fullStr | Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title_full_unstemmed | Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title_short | Transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| title_sort | transplanted erythropoietin-expressing mesenchymal stem cells promote pro-survival gene expression and protect photoreceptors from sodium iodate-induced cytotoxicity in a retinal degeneration model |
| url | http://psasir.upm.edu.my/id/eprint/93428/ http://psasir.upm.edu.my/id/eprint/93428/ http://psasir.upm.edu.my/id/eprint/93428/1/Transplanted%20erythropoietin-expressing.pdf |