Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA; Department of Biomedical Engineering, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA.
Department of Biomedical Science, University of Illinois College of Medicine, Rockford, IL, USA.
Acta Biomater. 2021 Oct 1;133:126-138. doi: 10.1016/j.actbio.2021.07.075. Epub 2021 Aug 5.
Hydrogels have been used to design synthetic matrices that capture salient features of matrix microenvironments to study and control cellular functions. Recent advances in understanding of both extracellular matrix biology and biomaterial design have shown that biophysical cues are powerful mediators of cell biology, especially that of mesenchymal stromal cells (MSCs). MSCs have been tested in many clinical trials because of their ability to modulate immune cells in different pathological conditions. While roles of biophysical cues in MSC biology have been studied in the context of multilineage differentiation, their significance in regulating immunomodulatory functions of MSCs is just beginning to be elucidated. This review first describes design principles behind how biophysical cues in native microenvironments influence the ability of MSCs to regulate immune cell production and functions. We will then discuss how biophysical cues can be leveraged to optimize cell isolation, priming, and delivery, which can help improve the success of MSC therapy for immunomodulation. Finally, a perspective is presented on how implementing biophysical cues in MSC potency assay can be important in predicting clinical outcomes. STATEMENT OF SIGNIFICANCE: Stromal cells of mesenchymal origin are known to direct immune cell functions in vivo by secreting paracrine mediators. This property has been leveraged in developing mesenchymal stromal cell (MSC)-based therapeutics by adoptive transfer to treat immunological rejection and tissue injuries, which have been tested in over one thousand clinical trials to date, but with mixed success. Advances in biomaterial design have enabled precise control of biophysical cues based on how stromal cells interact with the extracellular matrix in microenvironments in situ. Investigators have begun to use this approach to understand how different matrix biophysical parameters, such as fiber orientation, porosity, dimensionality, and viscoelasticity impact stromal cell-mediated immunomodulation. The insights gained from this effort can potentially be used to precisely define the microenvironmental cues for isolation, priming, and delivery of MSCs, which can be tailored based on different disease indications for optimal therapeutic outcomes.
水凝胶已被用于设计合成基质，以捕获基质微环境的显著特征，从而研究和控制细胞功能。对外基质生物学和生物材料设计的理解的最新进展表明，生物物理线索是细胞生物学的有力调节剂，尤其是间充质基质细胞（MSC）的生物学。由于其在不同病理条件下调节免疫细胞的能力，MSC 已在许多临床试验中进行了测试。虽然生物物理线索在 MSC 生物学中的作用已在多谱系分化的背景下进行了研究，但它们在调节 MSC 免疫调节功能方面的重要性才刚刚开始得到阐明。
这篇综述首先描述了天然微环境中的生物物理线索如何影响 MSC 调节免疫细胞产生和功能的能力背后的设计原则。然后，我们将讨论如何利用生物物理线索来优化细胞分离、启动和递送，这有助于提高 MSC 免疫调节治疗的成功率。最后，提出了在 MSC 效力测定中实施生物物理线索的重要性，这对于预测临床结果具有重要意义。
起源于间质的基质细胞已知通过分泌旁分泌介质在体内指导免疫细胞功能。这种特性已被用于开发基于间充质基质细胞（MSC）的治疗方法，通过过继转移来治疗免疫排斥和组织损伤，迄今为止，已有超过一千项临床试验进行了测试，但成功率不一。生物材料设计的进步使我们能够根据基质细胞在原位微环境中与细胞外基质的相互作用来精确控制生物物理线索。研究人员已开始利用这种方法来了解不同基质生物物理参数（如纤维取向、孔隙率、维度和粘弹性）如何影响基质细胞介导的免疫调节。
从这项工作中获得的见解有可能被用于精确定义 MSC 分离、启动和递送的微环境线索，这些线索可以根据不同的疾病指征进行定制，以获得最佳的治疗效果。
