Department of Orthopedic Surgery, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Korea.
These authors contributed equally to this work.
Mol Cells. 2021 Apr 30;44(4):245-253. doi: 10.14348/molcells.2021.0037.
Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 ()-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The gene was successfully inserted into a 'safe harbor' genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.
尽管间充质干细胞 (MSCs) 以软骨再生而闻名，但它们的治疗效果需要增强。在本研究中，我们生产了基因组编辑的沉默信息调节因子 2 型 1 ()-过表达 MSCs，并在受损软骨性肝纤维化模型中评估了它们的治疗潜力。成功地将 基因插入了羊膜间充质干细胞 (AMMs) 的“安全港”基因组位，通过定量 PCR 和组织学对 基因过表达 AMMs (AMM/S) 的软骨特性进行了表征。在胶原诱导性关节炎 (CIA) 小鼠模型中研究了治疗潜力。软骨细胞分化的 AMM/S 表达软骨特异性基因，并对番红 O 染色呈阳性。AMM/S 的移植减轻了 CIA 的进展，并抑制了 CIA 小鼠中 Th17 细胞的激活，同时增加了 Treg 细胞群体。在 AMM/S 注射关节组织中，促炎因子，如白细胞介素 (IL)-1β、IL-6、单核细胞趋化蛋白 (MCP)-1 和肿瘤坏死因子 (TNF)-α 显著降低。总之，基因组编辑的 AMM/S 可能代表了治疗和修复受损软骨或炎症性关节关节炎的安全且替代的治疗选择。
