Abstract
Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats. We report that HRPCs/HBMSCs combined transplantation maintains the electroretinogram results much better than HRPCs or HBMSCs single transplantations. The thickness of outer nuclear layer also presented a better outcome in the combined transplantation. Importantly, grafted cells in the combination migrated better, both longitudinally and latitudinally, than single transplantation. The photoreceptor differentiation of grafted cells in the retina of RCS rats receiving combined transplantation also showed a higher ratio than single transplantation. Finally, activation of microglia and the gliosis of Müller cells were more effectively suppressed in combined transplantation, indicating better immunomodulatory and anti-gliosis effects. Taken together, combining the transplantation of HRPCs and HBMSCs is a more effective strategy in stem cell-based therapy for retinal degenerative diseases.
Highlights
Umbilical cord blood, adult forebrain or hippocampus, embryonic or neonatal retina, olfactory bulb and adult retina, have been used in transplanting potential cells into the subretinal space (SRS)[16]
To verify that the cells that we harvested from fetal eye are HRPCs, we tested for the expression of Ki67, PAX6 and SOX2, and Nestin via immunocytochemistry
The results showed that, on passage 3, the positive percentages of PAX6, Nestin, SOX2 and GFAP were 90.46%, 97.86%, 95.35% and 0.02%, respectively (Fig. 1p–s), which was consistent with the immunofluorescence results
Summary
Umbilical cord blood, adult forebrain or hippocampus, embryonic or neonatal retina, olfactory bulb and adult retina, have been used in transplanting potential cells into the subretinal space (SRS)[16]. Many studies have been performed using combined transplantation of two different stem cells to treat diseases such as spinal cord injury, autism, diabetes, myocardial infarction and ischemia[32,33,34,35,36,37]. The results of these combined transplantation therapies presented good outcomes and no obvious side effects, indicating that combined transplantation is a safe and effective method. Using ERG, immunofluorescence, western-blot and RT-PCR, we assayed the efficacy of combined transplantation of these two cells
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