Date Posted: 04 November 2009
One of the biggest challenges in converting the promise of stem cell therapies into clinical use is to define the elixir that directs the embryonic stem cell to produce the desired fully differentiated specialised cell type. After much tinkering and a little luck researchers at the Hadassah-Hebrew University Medical Centre in Jerusalem have now reported the production of fully differentiated functioning RPE cells, cultured in the lab and delivered to animal models.
While many research groups are active in this field the major achievement by the Israeli group was the increase in the proportion of RPE cells produced from a stock of human embryonic stem cells. The "magical" ingredient bringing about such an increase appears to be nicotinamide (NIC) - a precursor of the co-enzyme beta-nicotinamide adenine dinucleotide [NAD+] involved in the production of ATP in the mitochondria. The apparently serendipitous addition of nicotinamide to floating embryoid bodies increased the number of observed developing pigmented areas from 13% to 78% after 8 weeks. While still a significant step away from a 100% pure RPE cell population, the increase represents a dramatic improvement on previous protocols.
Having produced RPE batches of cells expressing many markers of RPE biology the research team sub-retinally transplanted the stem cell-derived RPE cells into 3 week-old animal models of impaired retinal functioning (RCS Mertk rat). Within 6 weeks of treatment researchers observed an improved ERG and preservation of retinal function compared to controls. Follow-up analysis out to 13 weeks of age confirmed a significant functional rescue in addition to the encouraging finding that transplanted RPE cells appeared to be functioning healthily in respect of rod photoreceptor outer segment phagocyotisis. Dysfunctional and degenerating RPE cells are found in several retinal disorders including Best disease, sub-types of RP and in AMD, all of which may stand to benefit if the technology can be developed for human application [Idelson et al, Cell Stem Cell 5, 396-408, October 2, 2009].
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