Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
Biomater Sci. 2018 May 29;6(6):1445-1456. doi: 10.1039/c7bm00559h.
Dysfunctional salivary gland (SG) is an unsolved clinical challenge, which is presented as xerostomia. Cell therapy is a promising treatment for restoring SG function. Salispheres are spheroid cellular organizations derived from SG stem cells. Benefitting from these cellular organizations, SG stem cells can be expanded to regenerate SG. During in vitro culture, the spontaneous reorganization of salispheres may change the features of residing SG stem cells. Therefore, it is imperative to explore ways to maintain the spheroid structure of salispheres during cell expansion in vitro. Herein, we explored biomaterial approaches using chitosan. Chitosan based biomaterials were fabricated in different forms to offer distinct interactive surfaces for cultured salispheres. The number and size of the salispheres increase in the chitosan-containing systems without increasing the incidence of spheroid cavitation. The effect of chitosan increases with high chitosan concentrations, which is optimum when chitosan is fabricated in a soluble form. The chitosan effect contributes to the regulation of the intercellular interactions and polarization within the spheroid structures. By retarding the process of salisphere cavitation, chitosan preserves the features of salivary gland progenitor cells in the cultured salispheres. The results suggest that the chitosan-containing system could effectively maintain the primitive structures and properties of salispheres during in vitro expansion, which demonstrates the potential application of salispheres for cell therapy of dysfunctional SG.
唾液腺功能障碍是一个未解决的临床挑战，其表现为口干。细胞疗法是恢复唾液腺功能的一种有前途的治疗方法。唾液球体是由唾液腺干细胞衍生而来的球体细胞组织。得益于这些细胞组织，唾液腺干细胞可以被扩增以再生唾液腺。在体外培养过程中，唾液球体的自发重组可能会改变驻留唾液腺干细胞的特征。因此，探索在体外细胞扩增过程中维持唾液球体的球体结构的方法势在必行。在此，我们探索了使用壳聚糖的生物材料方法。壳聚糖基生物材料被制成不同的形式，为培养的唾液球体提供了不同的相互作用表面。在含有壳聚糖的系统中，唾液球体的数量和大小增加，而不会增加球体空洞的发生率。壳聚糖的作用随着壳聚糖浓度的增加而增加，当壳聚糖以可溶性形式制备时效果最佳。壳聚糖的作用有助于调节球体结构内的细胞间相互作用和极化。通过延缓唾液球体空洞化的过程，壳聚糖保留了培养的唾液球体中唾液腺祖细胞的特征。结果表明，含有壳聚糖的系统可以有效地在体外扩增过程中保持唾液球体的原始结构和特性，这证明了唾液球体在唾液腺功能障碍的细胞治疗中的潜在应用。
