PMID- 29210653 OWN - NLM STAT- MEDLINE DCOM- 20190611 LR - 20190613 IS - 1875-5666 (Electronic) IS - 1566-5240 (Linking) VI - 17 IP - 6 DP - 2017 TI - Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats. PG - 421-435 LID - 10.2174/1566524018666171205140806 [doi] AB - BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). OBJECTIVE: To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. METHODS: Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. RESULTS: Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. CONCLUSION: The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Wang, L AU - Wang L AD - Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. FAU - Li, P AU - Li P AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Tian, Y AU - Tian Y AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Li, Z AU - Li Z AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Lian, C AU - Lian C AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Ou, Q AU - Ou Q AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Jin, C AU - Jin C AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Gao, F AU - Gao F AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Xu, J-Y AU - Xu JY AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Wang, J AU - Wang J AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Wang, F AU - Wang F AD - Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. FAU - Zhang, J AU - Zhang J AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Zhang, J AU - Zhang J AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Li, W AU - Li W AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Tian, H AU - Tian H AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Lu, L AU - Lu L AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. FAU - Xu, G-T AU - Xu GT AD - Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Curr Mol Med JT - Current molecular medicine JID - 101093076 SB - IM MH - Animals MH - *Cell Differentiation MH - Cells, Cultured MH - Humans MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/classification/*cytology MH - Rats MH - Retinal Degeneration/*therapy MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Human umbilical cord mesenchymal stem cells OT - antiapoptotic effect OT - cell differentiation OT - paracrine. OT - retinal degeneration OT - stem cell subpopulation EDAT- 2017/12/07 06:00 MHDA- 2019/06/14 06:00 CRDT- 2017/12/07 06:00 PHST- 2017/06/19 00:00 [received] PHST- 2017/11/08 00:00 [revised] PHST- 2017/11/29 00:00 [accepted] PHST- 2017/12/07 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2017/12/07 06:00 [entrez] AID - CMM-EPUB-87263 [pii] AID - 10.2174/1566524018666171205140806 [doi] PST - ppublish SO - Curr Mol Med. 2017;17(6):421-435. doi: 10.2174/1566524018666171205140806.