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Kristan Worthington, Aliasger Salem, Allan Guymon, Budd Tucker; Controlled Physical Properties of Stem Cell Scaffolds for Photoreceptor Regeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4697.
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The degeneration of photoreceptors, as manifested in diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), is one of the leading causes of blindness in the western world. Injection of a single cell suspension into the sub-retinal space has been shown to partially restore function to retinas with early-stage degeneration. This success, however, does not translate to advanced disease due to low cell retention, viability and integration. In late stage disease injected cells overall lack the support necessary for restoring retinal function. The goal of this project is to provide support to differentiating replacement cells using an injectable stem cell scaffold with controlled physical properties.
Micro- and nano-porous cell scaffolds were synthesized by direct and lyotropic liquid crystalline (LLC) templating, respectively, of photopolymerizable pre-polymers. Pore size and density were controlled using microfabrication techniques and surfactant (LLC) type and concentration. These physical features were characterized using scanning electron microscopy (SEM), small-angle x-ray scattering (SAXS), and polarized light microscopy (PLM). To test the effects of the varying physical features, the scaffolds were seeded with murine induced pluripotent stem (MiPS) cells, which were differentiated for defined amounts of time and characterized with SEM and immunohistochemistry.
Scaffold physical features such as pore size and spacing were found to significantly influence the growth and differentiation of iPSCs. Similarly the presence of nanostructure, introduced via lyotropic liquid crystalline templating, improved the diffusion properties of the material and thus also positively influenced iPSC behavior. The optimized materials produced were shown to support the differentiation of induced pluripotent stem cells toward mature retinal cell phenotypes.
This work shows that physical properties of photopolymers can be successfully manipulated to meet the needs of photoreceptor regeneration applications. An optimized material of this kind; one that is biocompatible, implantable, and able to encourage growth and differentiation of mature retinal cell types, could lead to the successful transplantation of replacement cells and ultimately, restoration of retinal function in patients who suffer from late stage retinal degeneration.
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