Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Nat Commun. 2023 Nov 22;14(1):7639. doi: 10.1038/s41467-023-43239-6.
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.
虽然间充质干细胞 (MSCs) 因其自我更新、集落形成和分化潜能的独特特性而引起了极大的关注，但 MSC 分泌组因其在免疫调节、抗炎活性、血管生成和抗细胞凋亡中的作用而变得有吸引力。然而，精确刺激和高效生产 MSC 分泌组用于治疗应用是具有挑战性的问题。在这里，我们报告了用于 MSC 机械生物分泌组的声流界面：AIMS。我们创建了一个声流机械生物环境，以形成可重复的三维 MSC 聚集体，从而高效地产生 MSC 分泌组。我们通过 AIMS 证实增加的 MSC 分泌组是由于细胞间相互作用得到改善：关键介质 N-钙粘蛋白上调，而 N-钙粘蛋白的功能阻断则不会增强分泌组。在 IFN-γ 引发后，MSC 聚集体的分泌组谱包含更多抗炎细胞因子，可用于抑制 M1 表型巨噬细胞的促炎反应、抑制 T 细胞激活和支持 B 细胞功能。因此，MSC 分泌组可用于个性化的基于分泌组的治疗。AIMS 是一种强大的工具，可用于改善 MSC 分泌组并精确调整分泌谱，以在转化医学中开发新的治疗方法。
