Genetically-modified human mesenchymal stem cells to express erythropoietin enhances differentiation into retinal photoreceptors: An in-vitro study

Ding, Suet Lee Shirley; Koh, Avin Ee-Hwan; Kumar, Suresh; Khan, Mohammed Safwan Ali; Alzahrani, Badr; Mok, Pooi Ling

doi:10.1016/j.jphotobiol.2019.04.008

Cited by 13 publications

(15 citation statements)

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“…(Malaysia) in the form of cryovial, with written, informed consent from patient donors. The cells were cultureexpanded and characterized as described in previous publications from our laboratory (Ding et al 2019a). These cells were then transduced by lentiviral particles encoding EPO gene according to a procedure mentioned in a prior report (Ding et al 2019a).…”

Section: Materials and Methods Cell Culture And Characterization Of Mmentioning

confidence: 99%

“…The cells were cultureexpanded and characterized as described in previous publications from our laboratory (Ding et al 2019a). These cells were then transduced by lentiviral particles encoding EPO gene according to a procedure mentioned in a prior report (Ding et al 2019a). The transduced cells were cryopreserved in liquid nitrogen at -180°C until used for further experiments.…”

Section: Materials and Methods Cell Culture And Characterization Of Mmentioning

confidence: 99%

“…Tremendous works have been dedicated to research into possible use of Mesenchymal Stem Cells (MSCs) for countering visual loss in the elderly due to AMD (Ding et al 2019a;Mok et al 2017). MSCs represents a reliable cell source that has multipotent differentiation potential, within and beyond its mesodermal lineage, to form different cell types.…”

Section: Introductionmentioning

confidence: 99%

“…In our previous studies, we showed that when MSCs were transplanted into a transgenic rat model that exhibit retina degeneration, some of these cells formed retina neuronal cells (Leow et al 2015). In an in vitro study, we showed that these cells could be better coaxed into retinal photoreceptor cells when introduced with erythropoietin (EPO) gene (Ding et al 2019a). Similar to other studies that demonstrated successful MSC differentiation into other neuronal cells (Danielyan et al 2009;Hayashi 2013;Roozafzoon et al 2015), the limited photoreceptor cell yield remains one major obstacle in achieving sufficient visual function improvement.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, the current study is a follow-up initiative to find methods to upscale the production of photoreceptors in the laboratory (Ding et al 2019a). Instead of direct differentiation, we hypothesized that MSC-EPO could be differentiated into neurosphere before further induction to produce larger number of photoreptors.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Materials and Methods Cell Culture And Characterization Of Mmentioning

confidence: 99%

Section: Materials and Methods Cell Culture And Characterization Of Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%