期刊
TISSUE ENGINEERING PART C-METHODS
卷 21, 期 10, 页码 1032-1043出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tec.2014.0665
关键词
-
资金
- Zell Family Foundation
- Society for Surgery of the Alimentary Tract
- Robert R. McCormick Foundation
- Northwestern Memorial Foundation Dixon Translational Research Grants Initiative
- American Society of Transplant Surgeon's Faculty Development Grant
- National Kidney Foundation of Illinois
- American Association for the Study of Liver Diseases
- American Liver Foundation
- NIDDK [K08 DK10175, R01 DK050141, K01 DK097206]
- Dialysis Clinic, Inc.
- Northwestern University Microsurgery Core
- Northwestern University Mouse Histology and Phenotyping Laboratory
- SQI Equipment Core
- Cancer Center Support Grant [NCI CA060553]
Analysis of perfusion-based bioreactors for organ engineering and a detailed evaluation of physical and biochemical parameters that measure dynamic changes within maturing cell-laden scaffolds are critical components of ex vivo tissue development that remain understudied topics in the tissue and organ engineering literature. Intricately designed bioreactors that house developing tissue are critical to properly recapitulate the in vivo environment, deliver nutrients within perfused media, and monitor physiological parameters of tissue development. Herein, we provide an in-depth description and analysis of two dual-purpose perfusion bioreactors that improve upon current bioreactor designs and enable comparative analyses of ex vivo scaffold recellularization strategies and cell growth performance during long-term maintenance culture of engineered kidney or liver tissues. Both bioreactors are effective at maximizing cell seeding of small-animal organ scaffolds and maintaining cell survival in extended culture. We further demonstrate noninvasive monitoring capabilities for tracking dynamic changes within scaffolds as the native cellular component is removed during decellularization and model human cells are introduced into the scaffold during recellularization and proliferate in maintenance culture. We found that hydrodynamic pressure drop (P) across the retained scaffold vasculature is a noninvasive measurement of scaffold integrity. We further show that P, and thus resistance to fluid flow through the scaffold, decreases with cell loss during decellularization and correspondingly increases to near normal values for whole organs following recellularization of the kidney or liver scaffolds. Perfused media may be further sampled in real time to measure soluble biomarkers (e.g., resazurin, albumin, or kidney injury molecule-1) that indicate degree of cellular metabolic activity, synthetic function, or engraftment into the scaffold. Cell growth within bioreactors is validated for primary and immortalized cells, and the design of each bioreactor is scalable to accommodate any three-dimensional scaffold (e.g., synthetic or naturally derived matrix) that contains conduits for nutrient perfusion to deliver media to growing cells and monitor noninvasive parameters during scaffold repopulation, broadening the applicability of these bioreactor systems.
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