Wechsler Marissa E, Rao Varsha V, Borelli Alexandra N, Anseth Kristi S
Department of Chemical and Biological Engineering, University of Colorado-Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA.
BioFrontiers Institute, University of Colorado-Boulder, 3415 Colorado Avenue, Boulder, CO, 80303, USA.
Adv Healthc Mater. 2021 Apr;10(7):e2001948. doi: 10.1002/adhm.202001948. Epub 2021 Feb 17.
The therapeutic benefits of exogenously delivered mesenchymal stromal/stem cells (MSCs) have been largely attributed to their secretory properties. However, clinical translation of MSC-based therapies is hindered due to loss of MSC regenerative properties during large-scale expansion and low survival/retention post-delivery. These limitations might be overcome by designing hydrogel culture platforms to modulate the MSC microenvironment. Hydrogel systems could be engineered to i) promote MSC proliferation and maintain regenerative properties (i.e., stemness and secretion) during ex vivo expansion, ii) improve MSC survival, retention, and engraftment in vivo, and/or iii) direct the MSC secretory profile using tailored biochemical and biophysical cues. Herein, it is reviewed how hydrogel material properties (i.e., matrix modulus, viscoelasticity, dimensionality, cell adhesion, and porosity) influence MSC secretion, mediated through cell-matrix and cell-cell interactions. In addition, it is highlighted how biochemical cues (i.e., small molecules, peptides, and proteins) can improve and direct the MSC secretory profile. Last, the authors' perspective is provided on future work toward the understanding of how microenvironmental cues influence the MSC secretome, and designing the next generation of biomaterials, with optimized biophysical and biochemical cues, to direct the MSC secretory profile for improved clinical translation outcomes.
外源性递送的间充质基质/干细胞（MSC）的治疗益处很大程度上归因于其分泌特性。然而，基于MSC的疗法在临床转化中受到阻碍，原因是在大规模扩增过程中MSC的再生特性丧失，以及递送后存活率/保留率较低。通过设计水凝胶培养平台来调节MSC微环境，这些限制可能会被克服。水凝胶系统可以被设计成：i）在体外扩增过程中促进MSC增殖并维持其再生特性（即干性和分泌能力）；ii）提高MSC在体内的存活率、保留率和植入率；和/或iii）使用定制的生化和生物物理线索来引导MSC的分泌谱。本文综述了水凝胶材料特性（即基质模量、粘弹性、维度、细胞粘附和孔隙率）如何通过细胞-基质和细胞-细胞相互作用来影响MSC的分泌。此外，还强调了生化线索（即小分子、肽和蛋白质）如何改善和引导MSC的分泌谱。最后，作者对未来工作提出了展望，即了解微环境线索如何影响MSC分泌组，并设计具有优化生化和生物物理线索的下一代生物材料，以引导MSC分泌谱，从而改善临床转化结果。
