Characterization of adult human retinal stem cells
During embryogenesis, the neural retina, ciliary body (CB) and distal iris of the human eye are also formed from the multipotent stem cells of the neuroectoderm. In adults the retina has limited regenerative potential, and severe injuries will lead to permanent damage. However, recent studies have shown that the adult CB harbours a small population of progenitors with characteristics of neural stem cells that are quiescent in vivo but can be expanded in culture (Fig. 3). In a collaboration project with the Centre for Eye Research, Department of Ophthalmology, Ullevål University Hospital, Rebecca Frøen and Morten Moe are currently studying the differentiation properties of these cells with the purpose of determining their future potential usefulness in therapy of retinal disease.
This year we have published results from a study directly comparing human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized stem cell niche in the CNS of adults. We found that both CB and SVZ spheres contained a population of neural progenitors, but that CB spheres, as opposed to SVZ-spheres, also contained cells with an epithelial phenotype, as judged by morphology, ultrastructural characteristics, expression of epithelial markers, and downregulation of neural progenitor markers.
Our preliminary data also shows that cells from the human iris pigmented epithelium (IPE) form spheres in culture with similar properties to those derived from the CB. After induced differentiation, cells from both CB and IPE spheres acquire a mature neuronal morphology and strongly express more mature neuronal markers such as beta-III-tubulin and Map-2. A subpopulation of the beta-III-tubulin-positive cells also show robust expression of rhodopsin, a marker of mature photoreceptors.
These results suggest that spheres derived from the human CB and IPE have the ability to differentiate into neuronallike cells, including photoreceptors. In the coming year we will test these cells for functional properties of mature photoreceptors. The discovery that human IPE-cells have similar properties to CB-cells may be of potential clinical importance, since the IPE tissue is easily accessible from patient biopsies in a potential setting of autotransplantation.
This year we have published results from a study directly comparing human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized stem cell niche in the CNS of adults. We found that both CB and SVZ spheres contained a population of neural progenitors, but that CB spheres, as opposed to SVZ-spheres, also contained cells with an epithelial phenotype, as judged by morphology, ultrastructural characteristics, expression of epithelial markers, and downregulation of neural progenitor markers.
Our preliminary data also shows that cells from the human iris pigmented epithelium (IPE) form spheres in culture with similar properties to those derived from the CB. After induced differentiation, cells from both CB and IPE spheres acquire a mature neuronal morphology and strongly express more mature neuronal markers such as beta-III-tubulin and Map-2. A subpopulation of the beta-III-tubulin-positive cells also show robust expression of rhodopsin, a marker of mature photoreceptors.
These results suggest that spheres derived from the human CB and IPE have the ability to differentiate into neuronallike cells, including photoreceptors. In the coming year we will test these cells for functional properties of mature photoreceptors. The discovery that human IPE-cells have similar properties to CB-cells may be of potential clinical importance, since the IPE tissue is easily accessible from patient biopsies in a potential setting of autotransplantation.