Engineered renal tissues, arrays thereof, and methods of making the same
AssigneeOrganovo, Inc.
InventorsDeborah Lynn Greene Nguyen, Shelby Marie King, Sharon C. Presnell
Life of this patent
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Abstract
Disclosed are renal tissues and arrays thereof that include a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells; and a layer of renal epithelial tissue, the renal epithelial tissue comprising renal tubular epithelial cells, the renal epithelial tissue in contact with the layer of renal interstitial tissue to form a three-dimensional, engineered, biological renal tissue. Also disclosed are methods of fabricating and using the same.
Claims30
A three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
- (a) a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells;
- and
- (b) a layer of renal epithelial tissue, the renal epithelial tissue comprising renal tubular epithelial cells;
- and
- (c) a layer of basement membrane between the layer of renal interstitial tissue and the layer of renal epithelial tissue, to form the three-dimensional, engineered, biological renal tubule model;
- wherein the fibroblasts and endothelial cells are present in a ratio of fibroblasts to endothelial cells at which the renal tubule model is planar six days post-printing.
A three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
- (a) a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells;
- and
- (b) a layer of renal epithelial tissue, the renal epithelial tissue comprising polarized renal tubular epithelial cells, to form the three-dimensional, engineered, biological renal tubule model;
- wherein the fibroblasts and endothelial cells are present in a ratio of fibroblasts to endothelial cells at which the renal tubule model is planar six days post-printing.
A method of assessing the renal toxicity of a therapeutic agent, the method comprising:
- (a) contacting the therapeutic agent with a three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
- (i) a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells;
- and
- (ii) a layer of renal epithelial tissue, the renal epithelial tissue comprising renal tubular epithelial cells, to form the three-dimensional, engineered, biological renal tubule model;
- wherein the fibroblasts and endothelial cells are present in a ratio of fibroblasts to endothelial cells at which the renal tubule model is planar six days post-printing;
- (b) measuring viability or functionality of the renal tubular epithelial cells;
- and
- (c) assessing the renal toxicity of the therapeutic agent based on the measured viability or functionality of the renal tubular epithelial cells.
A method of testing the viability of tubular epithelial cells in the presence of a therapeutic agent, comprising:
- (a) contacting the therapeutic agent with a three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
- (i) a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells;
- and
- (ii) a layer of renal epithelial tissue, the renal epithelial tissue comprising renal tubular epithelial cells, to form the three-dimensional, engineered, biological renal tubule model;
- wherein the fibroblasts and endothelial cells are present in a ratio of fibroblasts to endothelial cells at which the renal tubule model is planar six days post-printing;
- (b) measuring gamma glutamyl-transferase (GGT) activity in the model compared to a control;
- and
- (c) wherein decreased GGT activity in the model compared to the control is indicative of reduced viability of the renal tubular epithelial cells.
A method of testing the effect of a therapeutic agent on a renal transport molecule, comprising
- (a) contacting the therapeutic agent with a three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
- (i) a layer of renal interstitial tissue, the renal interstitial tissue comprising renal fibroblasts and endothelial cells;
- and
- (ii) a layer of renal epithelial tissue, the renal epithelial tissue comprising renal tubular epithelial cells, to form the three-dimensional, engineered, biological renal tubule model;
- wherein the fibroblasts and endothelial cells are present in a ratio of fibroblasts to endothelial cells at which the renal tubule model is planar six days post-printing;
- and
- (b) measuring the transport molecule activity in the model compared to a control.
Dependencies are inferred from the claim text.