Development of human embryonic stem cell therapies for age-related macular degeneration

2013 ◽  
Vol 36 (7) ◽  
pp. 385-395 ◽  
Author(s):  
Amanda-Jayne F. Carr ◽  
Matthew J.K. Smart ◽  
Conor M. Ramsden ◽  
Michael B. Powner ◽  
Lyndon da Cruz ◽  
...  
2021 ◽  
Vol 10 (8) ◽  
pp. 1785
Author(s):  
Tadao Maeda ◽  
Sunao Sugita ◽  
Yasuo Kurimoto ◽  
Masayo Takahashi

Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this field increasingly important.


2019 ◽  
Vol 20 (4) ◽  
pp. 926 ◽  
Author(s):  
Mária Szatmári-Tóth ◽  
Tanja Ilmarinen ◽  
Alexandra Mikhailova ◽  
Heli Skottman ◽  
Anu Kauppinen ◽  
...  

Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. We propose human embryonic stem cell-derived-RPE cells as a new model for studying RPE cell removal by professional phagocytes. The characteristics of human embryonic stem cells-derived RPE (hESC-RPE) are similar to native RPEs based on their gene and protein expression profile, integrity, and barrier properties or regarding drug transport. However, no data exist about RPE death modalities and how efficiently dying hESC-RPEs are taken upby macrophages, and whether this process triggers an inflammatory responses. This study demonstrates hESC-RPEs can be induced to undergo anoikis or autophagy-associated cell death due to extracellular matrix detachment or serum deprivation and hydrogen-peroxide co-treatment, respectively, similar to primary human RPEs. Dying hESC-RPEs are efficiently engulfed by macrophages which results in high amounts of IL-6 and IL-8 cytokine release. These findings suggest that the clearance of anoikic and autophagy-associated dying hESC-RPEs can be used as a new model for investigating AMD pathogenesis or for testing the in vivo potential of these cells in stem cell therapy.


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