期刊
TISSUE ENGINEERING PART A
卷 25, 期 13-14, 页码 1013-1022出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2018.0182
关键词
renal tubule cell; matrix elasticity; NHE3
资金
- NCI NIH HHS [P30 CA068485] Funding Source: Medline
- NEI NIH HHS [P30 EY008126] Funding Source: Medline
- NIBIB NIH HHS [U01 EB021214, U01 EB025136] Funding Source: Medline
- NIDDK NIH HHS [R01 DK062794, P30 DK020593, R03 DK110399, T32 DK007569, R01 DK051265, P30 DK114809, U2C DK059637, R01 DK108968, R01 DK095785, U24 DK059637, P30 DK058404, K01 DK092357, R24 DK103067, R01 DK069921] Funding Source: Medline
- BLRD VA [I01 BX003425, I01 BX002198] Funding Source: Medline
End-stage renal disease afflicts similar to 750,000 Americans and claims >100,000 lives annually in the United States. Kidney transplantation is associated with longest survival and least cost but is limited by scarcity of donor organs. The balance of patients are treated with dialysis, a cumbersome, morbid, and expensive procedure. Each hemodialysis treatment consumes in excess of 160 liters of water and anchors the patient to a machine for 12-15 h per week. Cultured tubule cells can reduce the obligate fluid requirements of a bioengineered artificial kidney by concentrating wastes and reabsorbing filtered salt and water. Primary tubule epithelial cells rapidly dedifferentiate in culture and form a flattened epithelium lacking the brush border essential to apicobasal transport. We hypothesized that substrate mechanical properties have a strong influence on differentiation in primary cell culture. We cultured primary renal tubule cells on polyacrylamide hydrogels of varying elasticity and measured expression of key transporter proteins essential to renal tubule cell function. Primary tubule cells cultured on soft substrates for extended periods showed increased expression of key transporters characteristic of differentiated proximal tubule cells. These data support the hypothesis that scaffold elasticity is a critical factor in cell culture, and, unexpectedly, that prolonged culture of primary cells was essential to observing this difference. Impact Statement Successful clinical tissue engineering requires functional fidelity of the cultured cell to its in vivo counterpart, but this has been elusive in renal tissue engineering. Typically, renal proximal tubule cells in culture have a flattened morphology and do not express key transporters essential to their function. In this article, we show for the first time that in vitro substrate mechanical properties dictate differentiation of cultured renal proximal tubule cells. Remarkably, this effect was only discernable after 4 weeks in culture, longer than usually reported for this cell type. These results demonstrate a new tunable parameter to optimize cell differentiation in renal tissue engineering.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据