Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa.
Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa.
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DOI：
10.1186/s13287-022-02828-w
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发表时间：
2022-04-08
影响因子：
7.5
通讯作者：
Chaudhry GR
中科院分区：
文献类型：
--
作者：
Brown C;Agosta P;McKee C;Walker K;Mazzella M;Alamri A;Svinarich D;Chaudhry GR
目前，还没有治疗视网膜退行性疾病(RDD)的方法，如视网膜色素变性(RP)。基于干细胞的疗法可以提供修复受损视网膜和恢复视力的有希望的机会。到目前为止，主要是成人间充质干细胞(MSCs)在临床前和临床研究中进行了研究，结果并不令人信服。我们应用了一种新的方法，即检测原始的(P)MSC来源的视网膜前体细胞(RPC)来治疗RD12小鼠RP模型的视网膜变性。用PKH26标记的PMSCs和RPC经玻璃体腔注射入RD12小鼠体内。用视网膜电图仪分析移植动物的视力和视网膜功能。细胞移植后4周和8周处死动物，进行视网膜的组织学、免疫学、分子和转录分析。移植的RPC显著改善了RD12小鼠的视力和视网膜厚度以及功能。PMSCs和RPC定位于不同的视网膜层。PMSCs归巢于视网膜色素上皮，RPC迁移到视网膜的神经层，在那里它们改善了各自层的厚度，并表达了细胞特异性标记。RPC可诱导抗炎和神经保护反应，并上调神经发生相关基因的表达。转录学分析表明，RPC通过抑制BMP，激活JAK/STAT和MAPK信号通路，促进视网膜神经发生和功能恢复。我们的研究表明，RPC可以对抗炎症，提供视网膜保护，并促进神经再生，从而改善RD12小鼠的视网膜结构和生理功能。网上版载有补充材料，可在10.1186/s13287-022-02828-w查阅。
Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP. Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina. Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways. Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice. The online version contains supplementary material available at 10.1186/s13287-022-02828-w.
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影响因子：
1.6
作者：
Hao X;Cheng J;Zhang Z
通讯作者：
Zhang Z
影响因子：
5.3
作者：
Kim, Gyu Hyun;Paik, Sun-Sook;Kim, In-Beom
通讯作者：
Kim, In-Beom
影响因子：
3.6
作者：
Das G;Choi Y;Sicinski P;Levine EM
通讯作者：
Levine EM
人类沃顿商学院果冻源间充质干细胞治疗视网膜变性的安全性和有效性。
影响因子：
3.7
作者：
Leow SN;Luu CD;Hairul Nizam MH;Mok PL;Ruhaslizan R;Wong HS;Wan Abdul Halim WH;Ng MH;Ruszymah BH;Chowdhury SR;Bastion ML;Then KY
通讯作者：
Then KY
影响因子：
16.8
作者：
Gao HM;Hong JS
通讯作者：
Hong JS