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
Estimating the term…
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.
Claims20
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 from a subject with a disease that affects kidney function,
- 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 renal 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 from a subject with a disease that affects kidney function,
- 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 gamma glutamyl-transferase (GGT) activity in the renal tubule model that has been contacted with the therapeutic agent compared to a control renal tubule model that has not been contacted with the therapeutic agent;
- wherein decreased GGT activity in the renal tubule model that has been contacted with the therapeutic agent compared to the control renal tubule model 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 from a subject with a disease that affects kidney function,
- 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 renal tubule model that has been contacted with the therapeutic agent compared to a control renal tubule model that has not been contacted with the therapeutic agent.
Dependencies are inferred from the claim text.