Editors' ChoiceRegenerative Medicine

Retinal Stem Cells: Eye Know Where to Go

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Science Translational Medicine  03 Mar 2010:
Vol. 2, Issue 21, pp. 21ec36
DOI: 10.1126/scitranslmed.3001003

The progression to blindness from retinal disease conjures images of the elderly adjusting to life with macular degeneration. But retinal maladies and their associated vision loss can strike in the prime of life, caused by conditions such as diabetic retinopathy or retinitis pigmentosa, which primarily affects the young. Current therapies mostly involve the use of growth factors or other bioactive molecules, with the goal of limiting disease progression rather than restoring retinal function. Now, in a recent issue of Biomaterials Ballios et al. describe a reagent designed to heal the damaged tissues.

With both age-related macular degeneration and retinitis pigmentosa, photoreceptor cells are lost, but the retinal microstructure remains intact. It should thus be possible to regenerate vision by replacing the damaged photoreceptors through stem-cell transplantation. In mice, adult retinal stem cells can differentiate into all types of retinal cells and will integrate into the developing eyes of early postnatal mice. Challenges associated with injecting stem cells into the eye include ensuring their survival during the injection process, preventing leakage from the injection site, and a lack of integration into the target tissue. Solid biomaterial scaffolds have been used to overcome these problems, but they tend to have a different stiffness and flexibility than the retina, making subretinal delivery a challenge and raising the risk of physical damage to the eye. The authors developed an injectable, biodegradable hydrogel based on hyaluronan and methylcellulose (HAMC), in which the HA promotes wound healing and the MC gives strength to the hydrogel in the form of physical crosslinks. In contrast with the transplantation of stem cells in a saline carrier, use of the viscous HAMC solution as a delivery medium for retinal stem cells injected into the eyes of mice ensured more uniform distribution of the cells, with less subsequent aggregation, and also promoted cellular distribution in the subretinal space. The HAMC-injected stem cells also integrated into the mouse retinal pigmented epithelium and adopted the native cuboidal morphology. The next hurdle will be to show that population of the retinal pigmented epithelium with stem cells restores the eye’s functionality.

B. G. Ballios et al., A hydrogel-based stem cell delivery system to treat retinal degenerative diseases. Biomaterials 31, 2555–2564 (2010). [Abstract]

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