Ophthalmology Department, First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
Sci Transl Med. 2020 Sep 23;12(562). doi: 10.1126/scitranslmed.aaw1120.
Stem cell therapy holds promises for treating corneal scarring. Here, we use multilineage-differentiating stress-enduring (Muse) cells to study their differentiation and therapeutic potential for treating corneal injury. Muse cells were isolated from lipoaspirate, which presented biphenotype properties of both pluripotent stem cells and some mesenchymal stem cells. Muse cells expanded by about 100-fold from the initial seeding cell number to Muse spheroids with the maintenance of the Muse cell phenotype and high cell viability at 33 days by static spheroid culture. We revealed that Muse spheroids were activated by the dynamic rotary cell culture system (RCCS), as characterized by increased stemness, improved activity, and enhanced adherence. Gene and protein expression of the pluripotent markers OCT3/4, SOX2, and NANOG and of the proliferation marker KI67 in Muse spheroids cultured under RCCS were higher than those in the static group. These activated Muse spheroids enabled ready differentiation into corneal stromal cells (CSCs) expressing characteristic marker genes and proteins. Furthermore, implantation of Muse cells-differentiated CSCs (Muse-CSCs) laden assembled with two orthogonally stacked stretched compressed collagen (cell-SCC) in mouse and tree shrew wounded corneas prevented the formation of corneal scarring, increased corneal re-epithelialization and nerve regrowth, and reduced the severity of corneal inflammation and neovascularization. cell-SCC retained the capacity to suppress corneal scarring after long-distance cryopreserved transport. Thus, Muse cell therapy is a promising avenue for developing therapeutics for treating corneal scarring.
干细胞疗法有望治疗角膜瘢痕。在这里，我们使用多能诱导分化应激耐受（Muse）细胞来研究其分化能力和治疗角膜损伤的潜力。Muse 细胞从脂肪抽吸物中分离出来，具有多能干细胞和一些间充质干细胞的双表型特性。Muse 细胞通过静态球体培养，在 33 天内从初始接种细胞数扩增约 100 倍，形成 Muse 球体，同时保持 Muse 细胞表型和高细胞活力。我们发现，Muse 球体通过动态旋转细胞培养系统（RCCS）被激活，其特征是干性增加、活性提高和黏附增强。在 RCCS 中培养的 Muse 球体中的多能标志物 OCT3/4、SOX2 和 NANOG 以及增殖标志物 KI67 的基因和蛋白表达均高于静态组。这些被激活的 Muse 球体能够轻易分化为表达特征性标记基因和蛋白的角膜基质细胞（CSCs）。此外，在小鼠和树鼩受伤角膜中植入负载组装有两个正交堆叠拉伸压缩胶原（细胞-SCC）的 Muse 细胞分化的 CSCs（Muse-CSCs），可防止角膜瘢痕形成，增加角膜再上皮化和神经再生，并减轻角膜炎症和新生血管形成的严重程度。细胞-SCC 在长途冷冻保存运输后仍保留抑制角膜瘢痕形成的能力。因此，Muse 细胞疗法是开发治疗角膜瘢痕治疗方法的有前途的途径。
