Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs.
Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs.
复制标题
DOI：
10.1038/s41467-023-43239-6
复制
发表时间：
2023-11-22
影响因子：
16.6
通讯作者：
Huang, Tony Jun
中科院分区：
文献类型：
--
作者：
He, Ye;Yang, Shujie;Liu, Pengzhan;Li, Ke;Jin, Ke;Becker, Ryan;Zhang, Jinxin;Lin, Chuanchuan;Xia, Jianping;Ma, Zhehan;Ma, Zhiteng;Zhong, Ruoyu;Lee, Luke P.;Huang, Tony Jun
间充质干细胞(MSCs)因其独特的自我更新、集落形成和分化潜能而备受关注，而MSC分泌体因其在免疫调节、抗炎、血管生成和抗凋亡等方面的作用而备受关注。然而，MSC分泌组的精确刺激和高效生产用于治疗应用是具有挑战性的问题。在这里，我们报告了针对MSCs的机械生物学分泌组的声流控界面：AIMS。我们创造了一个声流控的机械生物环境，形成了可重复的三维MSC聚集体，从而高效地产生了MSC分泌体。我们证实MSC分泌组的增加是由于使用AIMS改善了细胞-细胞间的相互作用：关键介质N-钙粘素上调，而功能阻断N-钙粘素则没有导致分泌组的增强。经干扰素-γ激活后，骨髓间充质干细胞聚集物的分泌组含有更多的抗炎细胞因子，可用于抑制M1表型巨噬细胞的促炎反应，抑制T细胞激活，并支持B细胞功能。因此，MSC分泌组可以被修改以用于基于分泌组的个性化治疗。AIMS是改善MSC分泌组和精确调整分泌组以开发转化医学新疗法的有力工具。高效生产治疗应用的MSC分泌组仍然是一项具有挑战性的任务。在这里，作者提出了一种方法，通过这种方法，声流控机械生物环境可以形成可复制的3D MSC聚集体，从而允许高效地生产分泌体。
While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine. Efficient production of MSC secretome for therapeutic applications remains a challenging task. Here, the authors present an approach whereby an acoustofluidic mechanobiological environment can form reproducible 3D MSC aggregates, allowing for secretome production with high efficiency.
登录
查看更多内容
影响因子：
5
作者：
Arifka M;Wilar G;Elamin KM;Wathoni N
通讯作者：
Wathoni N
声表面波微流控边界驱动流动的三维数值模拟与实验研究
影响因子：
6.1
作者：
Chen C;Zhang SP;Mao Z;Nama N;Gu Y;Huang PH;Jing Y;Guo X;Costanzo F;Huang TJ
通讯作者：
Huang TJ
影响因子：
5.9
作者：
Ambattu LA;Ramesan S;Dekiwadia C;Hanssen E;Li H;Yeo LY
通讯作者：
Yeo LY
影响因子：
5.5
作者：
Harman RM;Marx C;Van de Walle GR
通讯作者：
Van de Walle GR
影响因子：
5.2
作者：
de Klerk E;Hebrok M
通讯作者：
Hebrok M