Human mesenchymal stromal cells (hMSCs) are a promising cell source for numerous regenerative medicine and cell therapy-based applications. However, MSC-based therapies have faced challenges in translation to the clinic, in part due to the lack of sufficient technologies that accurately predict MSC potency and are viable in the context of cell manufacturing. Microfluidic platforms may provide an innovative opportunity to address these challenges by enabling multiparameter analyses of small sample sizes in a high throughput and cost-effective manner, and may provide a more predictive environment in which to analyze hMSC potency. To this end, we demonstrate the feasibility of incorporating 3D culture environments into microfluidic platforms for analysis of hMSC secretory response to inflammatory stimuli and multi-parameter testing using cost-effective and scalable approaches. We first find that the cytokine secretion profile for hMSCs cultured within synthetic poly(ethylene glycol)-based hydrogels is significantly different compared to those cultured on glass substrates, both in growth media and following stimulation with IFN-γ and TNF-α, for cells derived from two donors. For both donors, perfusion with IFN-γ and TNF-α leads to differences in secretion of interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), and interleukin-1 receptor antagonist (IL-1ra) between hMSCs cultured in hydrogels and those cultured on glass substrates. We then demonstrate the feasibility of analyzing the response of hMSCs to a stable concentration gradient of soluble factors such as inflammatory stimuli for potential future use in potency analyses, minimizing the amount of sample required for dose-response testing.

中文翻译：

---

使用可扩展平台启用间充质基质细胞免疫调节分析。

人间质基质细胞（hMSCs）是用于许多再生医学和基于细胞疗法的应用的有前途的细胞来源。然而，基于MSC的疗法在向临床翻译方面面临挑战，部分原因是缺乏足够的技术来准确预测MSC的效力，并且在细胞生产中是可行的。微流体平台可以通过以高通量和高性价比的方式对小样本量进行多参数分析来提供创新的机会来应对这些挑战，并可以提供更具预测性的环境来分析hMSC的效力。为此，我们证明了将3D培养环境整合到微流体平台中的可行性，以使用经济高效且可扩展的方法来分析hMSC对炎症刺激的分泌反应和多参数测试。我们首先发现，在合成聚（乙二醇）基水凝胶中培养的hMSC的细胞因子分泌特征与在玻璃基质中培养的hMSC相比，在生长培养基中以及在用IFN-γ和TNF-α刺激后，对于细胞而言，均显着不同。来自两个捐助者。对于这两个供体，灌注IFN-γ和TNF-α会导致白介素6（IL-6），白介素8（IL-8），单核细胞趋化蛋白1（MCP-1），巨噬细胞集落刺激因子的分泌差异（M-CSF），和在水凝胶中培养的hMSC与在玻璃基质上培养的hMSC之间的白介素-1受体拮抗剂（IL-1ra）。然后，我们证明了分析hMSC对可溶性因子（例如炎性刺激物）稳定浓度梯度的反应的可行性，以供将来在效能分析中使用，从而最大程度地减少了剂量反应测试所需的样品量。