Cell-Derived Extracellular Matrix-Rich Biomimetic Substrate Supports Podocyte Proliferation, Differentiation, and Maintenance of Native Phenotype

Cell-Derived Extracellular Matrix-Rich Biomimetic Substrate Supports Podocyte Proliferation, Differentiation, and Maintenance of Native Phenotype
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DOI:
10.1002/adfm.201908752
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发表时间:
2020-02-19
影响因子:
19
通讯作者:
Tsokos, George C.
Tsokos, George C.
中科院分区:
材料科学1区
文献类型:
--
作者:
Satyam, Abhigyan;Tsokos, Maria G.;Tsokos, George C.

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目前的技术和可用的支架材料不支持足细胞的长期细胞活力、分化和维持,足细胞是负责血液过滤的超专业肾脏驻留细胞。开发了一个新平台,通过对大分子拥挤表面上生长的成纤维细胞进行脱细胞来模仿天然肾脏微环境。与在组织培养塑料表面上培养的足细胞相比,在该平台上培养的人类永生化足细胞显示出长达 28 天的优越活力和代谢活性。新平台显示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/交叉指状结构的良好发展,与成熟一致。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。
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. A new platform which imitates the native kidney microenvironment by decellularizing fibroblasts grown on surfaces with macromolecular crowding is developed. Human immortalized podocytes cultured on this platform display superior viability and metabolic activity up to 28 days compared to podocytes cultured on tissue culture plastic surfaces. The new platform displays a softer surface and an abundance of growth factors and associated molecules. More importantly, it enables 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.