Exploitation of human mesenchymal stromal cell derived matrix towards the structural and functional restoration of the ocular surface
Exploitation of human mesenchymal stromal cell derived matrix towards the structural and functional restoration of the ocular surface
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利用人间充质基质细胞衍生基质修复眼表的结构和功能
DOI：
10.1039/d0bm00787k
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Fu Y.
中科院分区：
文献类型：
--
作者：
Yan D;Yan C;Yu F;Zhang S;Chen L;Wu N;Shao C;Yao Q;Sun H;Fu Y.
结膜修复是必不可少的，以帮助维持眼表微环境分泌润滑粘蛋白。然而，由于涉及疾病传播和同种异体反应性的风险，传统的羊膜移植治疗在其应用中具有许多限制。由于脱细胞组织已被频繁地用于组织工程和脂肪间充质干细胞（ADMSCs）已被公认为其低免疫原性，我们制作了脂肪来源的间充质基质细胞（DMA）的脱细胞基质，以研究DMA在愈合结膜缺损中的治疗潜力。在本研究中，制造的DMA，具有一定的厚度，在体内表现出移植的可操作性。当应用于结膜缺损兔模型时，DMA片在提供结构支撑方面发挥了实质性作用，而不会引起外观差异。此外，DMA在促进更快的伤口闭合方面显示出极大的优势，其具有比羊膜（AM）更好的含有更多杯状细胞的复层上皮。从机制上讲，与组织培养板（TCP）和胶原蛋白或纤连蛋白（DMA的两种主要成分）包被的TCP相比，DMA在维持CjECs干细胞处于未分化状态方面表现出其独特的性质，这对于长期结膜重建至关重要。此外，DMA通过激活Akt信号通路的更强磷酸化而有效地促进CjECs的增殖，其结果通过DMA重建的结膜上皮中p-Akt水平的组织学检查在体内实验中得到进一步验证。因此，ADMSC的脱细胞基质描绘了眼重建中有希望的结膜替代物。
Conjunctival restoration is indispensable to help maintain the ocular surface microenvironment by secreting lubricative mucins. However, conventional amniotic membrane transplantation therapy has many limitations in its application due to risks involved with disease transmission and alloreactivity. As decellularized tissues have been frequently used for tissue engineering and adipose mesenchymal stem cells (ADMSCs) have been acknowledged for their low immunogenicity, we fabricated a decellularized matrix of adipose-derived mesenchymal stromal cells (DMA) to study the therapeutic potential of DMA in healing conjunctival defects. In the present study, the fabricated DMA, with certain thickness, exhibited transplantation operability in vivo. When applied in conjunctival defect rabbit models, the sheet of DMA played a substantial role in providing structural support without causing cosmetic difference. Moreover, DMA displayed great superiority in promoting faster wound closure with better stratified epithelium containing more goblet cells than the amniotic membranes (AMs). Mechanistically, compared with the tissue culture plates (TCPs) and TCPs coated with collagen or fibronectin (two of the main components of DMA), DMA exhibited its unique property in maintaining the stem cells of CjECs in an undifferentiated state, which is highly essential for long-term conjunctival reconstruction. In addition, DMA effectively enhanced the proliferation of CjECs by activating stronger phosphorylation of the Akt signaling pathway, the results of which were further verified in the in vivo experiment via the histological examination of p-Akt levels in reconstructed conjunctival epithelium by DMA. Thus, the decellularized matrix of ADMSCs depicts a promising conjunctival substitute in ocular reconstruction.