Engineered renal tissues, arrays thereof, and methods of making the same
First Claim
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1. 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.
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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.
108 Citations
30 Claims
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1. A three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
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(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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A three-dimensional, engineered, bioprinted, biological renal tubule model comprising:
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(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. - View Dependent Claims (15, 16)
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17. A method of assessing the renal toxicity of a therapeutic agent, the method comprising:
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(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. - View Dependent Claims (18, 19, 20)
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21. A method of testing the viability of tubular epithelial cells in the presence of a therapeutic agent, comprising:
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(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. - View Dependent Claims (22, 23, 24)
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25. 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. - View Dependent Claims (26, 27, 28, 29, 30)
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Specification