Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration

• Published in: Cell death & disease 2022-09, Vol.13 (9), p.785-785, Article 785
• Main Authors: Zhu, Xiaoman, Chen, Zhiyang, Wang, Li, Ou, Qingjian, Feng, Zhong, Xiao, Honglei, Shen, Qi, Li, Yingao, Jin, Caixia, Xu, Jing-Ying, Gao, Furong, Wang, Juan, Zhang, Jingfa, Zhang, Jieping, Xu, Zhiguo, Xu, Guo-Tong, Lu, Lixia, Tian, Haibin
• Format: Article
• Language: English
• Subjects: 13/100; 13/89; 13/95; 42; 42/47; 631/532/2074; 692/308/2171; Age; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; c-Myc protein; Cell Biology; Cell Culture; Cell therapy; Epithelial Cells - metabolism; Gene expression; Humans; Immunology; Internalization; Life Sciences; LIM-Homeodomain Proteins - metabolism; Macular degeneration; Macular Degeneration - metabolism; Macular Degeneration - therapy; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Myc protein; Pathophysiology; Phagocytes; Rats; Retina; Retinal degeneration; Retinal Degeneration - metabolism; Retinal Degeneration - therapy; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Retinal Pigments - metabolism; SIX gene family; Stem cell transplantation; Stem cells; Transcription factors; Transcription Factors - metabolism; Umbilical cord; Umbilical Cord - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05199-5

Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-β receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.