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人骨髓间充质干细胞与人视网膜祖细胞联合移植入 RCS 大鼠视网膜下腔。

Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats.

机构信息

Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.

Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China.

出版信息

Sci Rep. 2017 Mar 15;7(1):199. doi: 10.1038/s41598-017-00241-5.

DOI:10.1038/s41598-017-00241-5
PMID:28298640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5428026/
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.

摘要

色素性视网膜炎(RP)是一种遗传性视网膜疾病,其特征是光感受器的丧失。细胞移植已被临床应用于治疗 RP 患者。人视网膜祖细胞(HRPCs)和人骨髓间充质干细胞(HBMSCs)是两种常用于移植的干细胞。由于联合移植可能是整合两种干细胞类型优势的一种有前途的方法,我们将 HRPCs 和 HBMSCs 移植到皇家外科学院(RCS)大鼠的视网膜下腔(SRS)中。我们报告 HRPCs/HBMSCs 联合移植比 HRPCs 或 HBMSCs 单一移植更能维持视网膜电图结果。在外核层的厚度方面,联合移植也呈现出更好的结果。重要的是,与单一移植相比,组合中移植的细胞在纵向和横向都有更好的迁移。在接受联合移植的 RCS 大鼠视网膜中,移植细胞的光感受器分化也显示出比单一移植更高的比例。最后,在联合移植中,小胶质细胞的激活和 Muller 细胞的胶质增生得到了更有效的抑制,表明其具有更好的免疫调节和抗胶质增生作用。综上所述,将 HRPCs 和 HBMSCs 的移植相结合是一种更有效的基于干细胞的视网膜退行性疾病治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/ed961f30fb1d/41598_2017_241_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/caaae91e76ef/41598_2017_241_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/db45e2d93ccc/41598_2017_241_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/e031cd644f4e/41598_2017_241_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/ed961f30fb1d/41598_2017_241_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/caaae91e76ef/41598_2017_241_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/da1aa0225bae/41598_2017_241_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/7352c0caae33/41598_2017_241_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/9244a1e269eb/41598_2017_241_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/db45e2d93ccc/41598_2017_241_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/79a8ee68b11c/41598_2017_241_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/e031cd644f4e/41598_2017_241_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ea/5428026/ed961f30fb1d/41598_2017_241_Fig8_HTML.jpg

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