Satyam Abhigyan, Tsokos Maria G, Tresback Jason S, Zeugolis Dimitrios I, Tsokos George C
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, United States.
Center for Nanoscale Systems, Laboratory for Integrated Science and Engineering, Harvard University, Cambridge, MA, 02138, United States.
Adv Funct Mater. 2020 Oct 28;30(44). doi: 10.1002/adfm.201908752. Epub 2020 Feb 19.
Current technologies and available scaffold materials do not support long-term cell viability, differentiation and maintenance of podocytes, the ultra-specialized kidney resident cells that are responsible for the filtration of the blood. We developed a new platform which imitates the native kidney microenvironment by decellularizing fibroblasts grown on surfaces with macromolecular crowding. Human immortalized podocytes cultured on this platform displayed superior viability and metabolic activity up to 28 days compared to podocytes cultured on tissue culture plastic surfaces. The new platform displayed a softer surface and an abundance of growth factors and associated molecules. More importantly it enabled podocytes to display molecules responsible for their structure and function and a superior development of intercellular connections/interdigitations, consistent with maturation. The new platform can be used to study podocyte biology, test drug toxicity and determine whether sera from patients with podocytopathies are involved in the expression of glomerular pathology.
当前的技术和可用的支架材料无法支持足细胞的长期细胞活力、分化和维持,足细胞是肾脏中负责血液过滤的超特化驻留细胞。我们开发了一个新平台,通过使在具有大分子拥挤效应的表面上生长的成纤维细胞去细胞化,来模拟天然肾脏微环境。与在组织培养塑料表面培养的足细胞相比,在这个平台上培养的人永生化足细胞在长达28天的时间里表现出更高的活力和代谢活性。新平台呈现出更柔软的表面以及丰富的生长因子和相关分子。更重要的是,它使足细胞能够展示负责其结构和功能的分子,以及细胞间连接/指状交叉的良好发育,这与成熟过程一致。这个新平台可用于研究足细胞生物学、测试药物毒性,以及确定足细胞病患者的血清是否参与肾小球病理的表达。