Tissue Engineering Models of Polycystic Kidney Disease.
Ko, Wei-Che.
2012
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Abstract: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a
life-threatening monogenic disorder where innumerable cysts develop in the kidney, leading
to renal failure. There is no known cure, and animal studies, while beneficial, often yield
mixed results when translated to the human condition. Thus, new opportunities present
itself for the study of human ADPKD by utilizing tissue eng... read moreineering principles of disease
modeling. However, modeling cystic diseases in vitro presents
a unique challenge as cyst morphogenesis, in addition to complex intercellular
interactions, is also governed by synergistic spatial, mechanical and temporal effects.
This thesis reports the development of kidney-like tissue structures for normal and
diseased (cystic) states using commercially available human kidney cells. Gene silencing is
used to simulate autosomal dominant polycystic kidney disease, as inactivating mutations in
polycystins -1 and/or -2 are responsible for the disease in
vivo. Our system utilizes extracellular-matrix molecules infused in slow
degrading porous silk scaffolds, which provides a 3D microenvironment for proper cell
polarization (ECM), while exhibiting structural robustness and tension (silk scaffold). Our
results indicate development of cyst-like structures in a 3D environment, while also
demonstrating the respective normal and altered phenotypes concurrent with normal tissue
and patient-derived ADPKD tissue. The structural and functional features of kidney-like
tissue structures were further characterized based on distribution of E-cadherin,
N-cadherin, transport phenomena of 6-carboxyfluorescein, and cell-matrix interactions
through integrin signaling. Importantly, this 3D in vitro model may be further extended via
perfusion reactor for long term studies of ADPKD or other renal cystic diseases, and may
have beneficial use as a therapeutic drug screening tool.
Thesis (M.S.)--Tufts University, 2012.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Ronald Perrone, and Qiaobing Xu.
Keyword: Biomedical engineering.read less - ID:
- g445cr91r
- Component ID:
- tufts:20882
- To Cite:
- DCA Citation Guide EndNote
