Enhancement of Lymphangiogenesis by Human Mesenchymal Stem Cell Sheet
Enhancement of Lymphangiogenesis by Human Mesenchymal Stem Cell Sheet
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DOI：
10.1002/adhm.202200464
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发表时间：
2022-07-01
影响因子：
10
通讯作者：
Zhao, Feng
中科院分区：
文献类型：
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作者：
Jia, Wenkai;He, Weilue;Zhao, Feng
淋巴水肿治疗的人间质干细胞（HMSC）悬浮液的制备依赖于常规的酶消化方法，这严重破坏了细胞细胞和细胞 - 细胞细胞基质（ECM）连接，并且在移植后会极大地影响细胞的保留和植入。本研究的目的是评估HMSC分泌的ECM通过使用淋巴内皮细胞（LECS）和体内小鼠尾lymphedema模型的HMSC表的体外共培养模型来增强淋巴管生成的能力。结果表明，相对于HMSC对照组，HMSC分泌的ECM通过用作促进生长型生长因子储层和促进细胞再生活性，将淋巴毛细血管样结构的形成增加了1.2-3.6。 HMSC衍生的ECM增强了MMP-2介导的基质重塑，增加胶原蛋白IV和层粘连蛋白的合成，并促进淋巴微血管样结构的形成。将大鼠MSC板片段注入小鼠尾部淋巴水肿模型，通过刺激淋巴管生成和伤口闭合来证实HMSC衍生的ECM的益处。
Preparation of human mesenchymal stem cell (hMSC) suspension for lymphedema treatment relies on conventional enzymatic digestion methods, which severely disrupts cell-cell and cell-extracellular matrix (ECM) connections, and drastically impairs cell retention and engraftment after transplantation. The objective of the present study is to evaluate the ability of hMSC-secreted ECM to augment lymphangiogenesis by using an in vitro coculturing model of hMSC sheets with lymphatic endothelial cells (LECs) and an in vivo mouse tail lymphedema model. Results demonstrate that the hMSC-secreted ECM augments the formation of lymphatic capillary-like structure by a factor of 1.2-3.6 relative to the hMSC control group, by serving as a prolymphangiogenic growth factor reservoir and facilitating cell regenerative activities. hMSC-derived ECM enhances MMP-2 mediated matrix remodeling, increases the synthesis of collagen IV and laminin, and promotes lymphatic microvessel-like structure formation. The injection of rat MSC sheet fragments into a mouse tail lymphedema model confirms the benefits of the hMSC-derived ECM by stimulating lymphangiogenesis and wound closure.