Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration

Alsaeedi, Hiba Amer; Koh, Avin Ee-Hwan; Lam, Chenshen; Rashid, Munirah Binti Abd; Harun, Mohd Hairul Nizam; Saleh, Muhamad Fakhri bin Mohd; Teh, Seoh Wei; Luu, Chi D; Ng, Min Hwei; Isa, Hazlita Mohd; Leow, Sue Ngein; Then, K.; Bastion, Mae-Lynn Catherine; Mok, Pooi Ling; Muthuvenkatachalam, Bala Sundaram; Samrot, Antony V.; Swamy, K. B.; Nandakumar, Jaikumar; Kumar, Suresh

doi:10.1016/j.jphotobiol.2019.111561

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…Numerous studies have revealed that DPSCs could migrate to the lesion site, which accelerates tissue repair and regeneration [16,17]. In addition, DPSCs present easy access, low-risk immune rejection and fewer ethical issues; hence, they can be used as ideal gene vehicles with wide application prospects [18,19].…”

Section: Introductionmentioning

confidence: 99%

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis

Zhang

Nepal

et al. 2021

Stem Cell Res Ther

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Background Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC. Methods The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group. Results Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-β and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-α and INF-γ) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group. Conclusions The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.

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Section: Introductionmentioning

confidence: 99%

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis

Zhang

Nepal

et al. 2021

Stem Cell Res Ther

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“…It is also possible that cell death may occur by induction of oxidative stress (Sachdeva et al, 2014). Previous study have shown that it can react specifically with this cell type in many animal species [e.g., and rabbits (Shen et al, 2010), rats (Alsaeedi et al, 2019), and sheep (Nilsson et al, 1977)]. When added into the ARPE-19 cell culture, a loss of epithelial cell morphology could be observed within 24 h (Figure 1).…”

Section: Discussionmentioning

confidence: 95%

Mitigation of Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells in vitro by Transgenic Erythropoietin-Expressing Mesenchymal Stem Cells

Koh

Subbiah

Farhana

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSC) have shown promise in restoring the vision of patients in clinical trials. However, this therapeutic effect is not observed in every treated patient and is possibly due to the inefficacies of cell delivery and high cell death following transplantation. Utilizing erythropoietin can significantly enhance the regenerative properties of MSCs and hence improve retinal neuron survivability in oxidative stress. Hence, this study aimed to investigate the efficacy of conditioned medium (CM) obtained from transgenic human erythropoietin-expressing MSCs (MSCEPO) in protecting human retinal pigment epithelial cells from sodium iodate (NaIO3)-induced cell death. Human MSC and MSCEPO were first cultured to obtain conditioned media (CM). The IC50 of NaIO3 in the ARPE-19 culture was then determined by an MTT assay. After that, the efficacy of both MSC-CM and MSC-CMEPO in ARPE-19 cell survival were compared at 24 and 48 h after NaIO3 treatment with MTT. The treatment effects on mitochondrial membrane potential was then measured by a JC-1 flow cytometric assay. The MTT results indicated a corresponding increase in cell survivability (5–58%) in the ARPE-19 cell cultures. In comparison to MSC-CM, the use of conditioned medium collected from the MSC-CMEPO further enhanced the rate of ARPE-19 survivability at 24 h (P < 0.05) and 48 h (P < 0.05) in the presence of NaIO3. Furthermore, more than 90% were found viable with the JC-1 assay after MSC-CMEPO treatment, showing a positive implication on the mitochondrial dynamics of ARPE-19. The MSC-CMEPO provided an enhanced mitigating effect against NaIO3-induced ARPE-19 cell death over that of MSC-CM alone during the early phase of the treatment, and it may act as a future therapy in treating retinal degenerative diseases.

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“…Mesenchymal stem cells (MSCs) has emerged as a suitable choice for replacement of retinal cells, particularly the photoreceptors (Leow et al 2015) and retinal pigmented epithelial cells (Alsaeedi et al 2019), which are highly affected in AMD progression (Bhutto & Lutty 2012). Despite many reported methods to generate photoreceptors in vitro or direct cell transplantations (Ding et al 2017), achievement of treatment outcomes remained far from ideal.…”

Section: Resultsmentioning

confidence: 99%

Photoreceptor Therapy: Generation of Neurosphere-Like Cells from Human Mesenchymal Stem Cells Expressing Erythropoietin

Mok¹,

Ding²,

Farhana³

et al. 2020

JSM

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The loss of photoreceptors is a major concern implicated in age-macular degeneration (AMD), a type of neurodegenerative disorder. Failure to prescribe a suitable treatment due to the lack of understanding of the molecular pathogenesis, and limited capacity to compensate irreparably damaged photoreceptors in the retina have greatly contributed to the progression of visual dysfunction. Our previous study has shown that Mesenchymal Stem Cells (MSCs) expressing erythropoietin (EPO) could commit into photoreceptor cell lineage. However, the efficiency of cell differentiation is limited. The present study aims to explore the capacity of these MSCs to form neurospheres. The cells were transduced with lentiviral particles encoding for human EPO and green fluorescent protein (GFP) genes, culture-expanded and sorted before subjected for differentiation induction into neural precursor cells. Our results showed that MSC-EPO developed into larger neurosphere and expressed relatively higher expression of nestin compared with MSCs alone when cultured under neural induction medium. These preliminary findings suggested that MSC-EPO have greater neurogenic potential than MSCs alone. Further study is needed to evaluate the possibilities of neurosphere to delete differentiate into functional photoreceptor cells. We believe that the success of neurosphere expansion may potentially be useful in scaling up the manufacturing of photoreceptors in a shorter time and at an efficient cost for retinal cell replacement therapy.

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Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration

Cited by 22 publications

References 33 publications

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis

Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis

Mitigation of Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells in vitro by Transgenic Erythropoietin-Expressing Mesenchymal Stem Cells

Photoreceptor Therapy: Generation of Neurosphere-Like Cells from Human Mesenchymal Stem Cells Expressing Erythropoietin

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