Department of Biomedical Engineering, Texas A&M University, 101 Bizzell St, Emerging Technologies Building, College Station, TX, 77843, USA.
Department of Biomedical Engineering, Michigan Technological University, Minerals & Materials Building, 1400 Townsend Drive, Room 309, Houghton, MI, 44931, USA.
Adv Healthc Mater. 2022 Aug;11(16):e2200464. doi: 10.1002/adhm.202200464. Epub 2022 Jul 1.
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.
用于治疗淋巴水肿的人骨髓间充质干细胞（hMSC）悬浮液的制备依赖于常规的酶消化方法，该方法严重破坏了细胞-细胞和细胞-细胞外基质（ECM）的连接，并在移植后极大地损害了细胞的保留和植入。本研究的目的是评估 hMSC 分泌的 ECM 通过 hMSC 薄片与淋巴管内皮细胞（LEC）的体外共培养模型和体内小鼠尾淋巴水肿模型来增强淋巴管生成的能力。结果表明，与 hMSC 对照组相比，hMSC 分泌的 ECM 将淋巴管样毛细血管结构的形成增加了 1.2-3.6 倍，充当了促淋巴管生成生长因子的储存库并促进了细胞再生活动。MSC 衍生的 ECM 增强 MMP-2 介导的基质重塑，增加了胶原 IV 和层粘连蛋白的合成，并促进了淋巴管样微血管结构的形成。将大鼠 MSC 薄片片段注射到小鼠尾淋巴水肿模型中，通过刺激淋巴管生成和伤口闭合证实了 hMSC 衍生的 ECM 的益处。
