Abstract
BackgroundHuman umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP). However, intravenously infused cells may be blocked in the lung, increasing the risk of vascular obstruction, which needs to be optimized to further improve safety and efficacy.MethodsWe derived small UCMSCs (S-UCMSCs) from filtering UCMSCs with a 10-μm filter, and compared with UCMSCs by flow cytometry, directional differentiation culture and transcriptome sequencing. Then the S-UCMSCs and UCMSCs were intravenously infused in the Royal College Surgeons (RCS) rats to evaluate the safety and the efficacy.ResultsThe diameter of S-UCMSCs ranged from 5.568 to 17.231 μm, with an average diameter of 8.636 ± 2.256 μm, which was significantly smaller than that of UCMSCs. Flow cytometry, immunofluorescence and transcriptome sequencing demonstrated that the S-UCMSCs and UCMSCs were the same kind of MSCs, and the S-UCMSCs were more proliferative. After the S-UCMSCs and UCMSCs were intravenously infused into the Royal College of Surgeons (RCS) rats at a dose of 1 × 106 cells/rat, the S-UCMSCs blocked in the lungs were significantly fewer and disappeared more quickly than UCMSCs. The b wave of the flash electroretinogram was improved at 7 d, and the retinal outer nuclear layer thickness was thicker at 7 d and 14 d. The expression level of inflammation was inhibited, and the expression level of neurotrophic factors was upregulated in the retina and serum after transplantation.ConclusionsS-UCMSCs intravenous infusion was safer than UCMSCs and could delay retinal degeneration and protect visual function in RCS rats, which may be a preferable therapeutic approach for RP.
Highlights
Human umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP)
We aimed to explore whether the intravenous infusion of small UCMSCs (S-UCMSCs) into Royal College of Surgeons (RCS) rats, a retinal degeneration animal model, could reduce the number of blocked cells in the lungs and simultaneously protect visual function
After intravenous infusion of S-UCMSCs and UCMSCs into RCS rats through the tail vein, no abnormal reactions in daily dietary activities were observed, and no immune rejection or tumorigenesis in the retina were found by stretch preparation or frozen section throughout the 28 days
Summary
Human umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP). Intravenous infusion is a popular route for MSC transplantation in clinical trials [16, 17] For retinal disease, it is noninvasive, low-cost, convenient and avoids the probable complications caused by vitreous cavity and subretinal transplantation, such as proliferation of fibrous tissue and traction retinal detachment [18,19,20]. Our previous clinical trials reported that intravenous infusion of MSCs could maintain or partially improve the visual function of advanced RP patients and nonproliferative diabetic retinopathy patients, and no side effects or complications were observed during these treatments [15, 21]. Intraocular transplantation may not be the most suitable treatment for advanced RP
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