Immortalized Human Fetal Retinal Cells Retain Progenitor Characteristics and Represent a Potential Source for the Treatment of Retinal Degenerative Disease

Cell Transplantation

Article

John Greenwood¹  Anthony A. Vugler¹  Stephen E. Moss¹  Shazeen M. Hasan¹  Erik A. Miljan²  John D. Sinden² 

[1] Department of Cell Biology, UCL Institute of Ophthalmology, London, UK;ReNeuron, Guildford, UK;

关键词: Retina;    Progenitor cells;    Conditional immortalization;    Cellular therapy;   

DOI  :  10.3727/096368910X505477

 received in 2009-09-16, accepted in 2010-04-22,  发布年份 2010

来源: Sage Journals

【 摘 要 】

Human fetal retinal cells have been widely advocated for the development of cellular replacement therapies in patients with retinal dystrophies and age-related macular degeneration. A major limitation, however, is the lack of an abundant and renewable source of cells to meet therapeutic demand, although theoretically this may be addressed through the use of immortalized retinal progenitor cell lines. Here, we have used the temperature-sensitive tsA58 simian virus SV40 T antigen to conditionally immortalize human retinal progenitor cells isolated from retinal tissue at 10–12 weeks of gestation. We show that immortalized human fetal retinal cells retain their progenitor cell properties over many passages, and are comparable with nonimmortalized human fetal retinal cultures from the same gestational period with regard to expression of certain retinal genes. To evaluate the capacity of these cells to integrate into the diseased retina and to screen for potential tumorigenicity, cells were grafted into neonatal hooded Lister rats and RCS dystrophic rats. Both cell lines exhibited scarce integration into the host retina and failed to express markers of mature differentiated retinal cells. Moreover, although immortalized cells showed a greater propensity to survive, the cell lines demonstrated poor long-term survival. All grafts were infiltrated with host macrophage/microglial cells throughout their duration of survival. This study demonstrates that immortalized human fetal retinal progenitor cells retain their progenitor characteristics and may therefore have therapeutic potential in strategies that demand a renewable and consistent supply of donor cells for the treatment of degenerative retinal diseases.

【 授权许可】

Unknown   
© 2010 Cognizant Comm. Corp.

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