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Ifat Sher-Rosenthal, Adi Tzameret, Michael Belkin, Avraham Treves, Arnon Nagler, Ygal Rotenstreich; A new method for subretinal transplantation of human adult stem cells preserves retinal structure along the entire retina and rescues retinal function in a rat model of retinal dystrophies. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2242.
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To develop an improved subretinal transplantation system of human-derived bone marrow mesenchymal stem cell population (hBM-MSCs).
hBM-MSC cells (CD73+; CD90+, CD105+, CD45-) from healthy human donors were transplanted into the sub-retina of one eye of 69 RCS rats at p28 (0.25 million cells/eye). Ten RCS rats were subretinally injected with medium as control. Retinal function was tested by electroretinogram before and following transplantation for 22 weeks. Eyes were inoculated for histology analysis. To demonstrate efficiency and safety of the new transplantation method in a large animal model, cells were transplanted in New Zealand White Rabbits and Spectral Domain Optical Coherence Tomography (SD-OCT, Heidelberg) was used for eye imaging and detection of transplanted cells.
Transplanted cells were identified shortly after transplantation as a uniform sheet of cells distributed along most of the retina and the choroid in RCS rats. One week after transplantation, cells were confined to the subretinal space. A prolonged (up to p168) and statistically significant enhancement of retinal function following hBM-SC transplantation was demonstrated by electroretinogram analysis. These results correlated with histological analysis that revealed a significant preservation of retinal structure with increased number of photoreceptors in the outer nuclear layer along most of the retina. No immunosuppressant were used and long-term safety analysis demonstrated no gross or microscopic adverse effects of cell transplantation. Preliminary experiments in rabbits demonstrated efficient subretinal transplantation using this method.
In this study we showed for the first time that transplanting hBM-MSCs as a thin homogenous sub-retinal layer significantly reduced the rate of retinal degeneration. This new transplantation method may enhance host-graft interaction and causes less trauma to the host tissue and milder retinal detachment. Our findings suggest that hBM-SCs may represent an effective and safe treatment for retinal dystrophy diseases. Furthermore, implementation of this new transplantation technique may enhance the therapeutic effect of other cell-based therapies.
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