The maintenance and direction of stem cell lineage after implantation remains challenging for clinical translation. Aggregation and encapsulation into instructive biomaterials after preconditioning can bolster retention of differentiated phenotypes. Since these procedures do not depend on cell type or lineage, we hypothesized we could use a common, tunable platform to engineer formulations that retain and enhance multiple lineages from different cell populations. To test this, we varied alginate stiffness and adhesive ligand content, then encapsulated spheroids of varying cellularity. We used Design-of-Experiments to determine the effect of these parameters and their interactions on phenotype retention. The combination of parameters leading to maximal differentiation varied with lineage and cell type, inducing a 2-4-fold increase over non-optimized levels. Phenotype was also retained for 4 weeks in a murine subcutaneous model. This widely applicable approach can facilitate translation of cell-based therapies by instructing phenotype in situ without prolonged induction or costly growth factors.

中文翻译：

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定义水凝胶特性以指导谱系和细胞特异性间充质分化。


植入后干细胞谱系的维持和指导对于临床转化仍然具有挑战性。预处理后聚集并封装到指导性生物材料中可以促进分化表型的保留。由于这些程序不依赖于细胞类型或谱系，我们假设我们可以使用一个通用的、可调节的平台来设计配方，以保留和增强来自不同细胞群的多个谱系。为了测试这一点，我们改变了藻酸盐硬度和粘附配体含量，然后封装了不同细胞结构的球体。我们使用实验设计来确定这些参数及其相互作用对表型保留的影响。导致最大分化的参数组合随谱系和细胞类型的不同而变化，导致比非优化水平增加 2-4 倍。在小鼠皮下模型中，表型也保留了 4 周。这种广泛适用的方法可以通过原位指导表型来促进基于细胞的疗法的转化，而无需长时间的诱导或昂贵的生长因子。