Engineered intestinal tissue and uses thereof
AssigneeOrganovo, Inc.
InventorsKelsey Nicole Retting, Deborah Lynn Greene Nguyen, Lauran Madden
Life of this patent
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Abstract
Disclosed are methods of assessing the ability of a candidate therapeutic agent to reverse, reduce or prevent intestinal injury by a potential toxic agent using a three-dimensional, engineered, bioprinted, biological intestinal tissue model. Also disclosed are methods of assessing the effect of an agent on intestinal function, the method comprising contacting the agent with a three-dimensional, engineered, bioprinted, biological intestinal tissue model.
Claims22
A method of assessing the ability of a candidate therapeutic agent to reverse or reduce an intestinal disorder or injury, the method comprising:
- a. contacting a bioprinted intestinal tissue model with the candidate therapeutic agent, wherein the intestinal tissue model has a phenotype of an intestinal disorder or injury and comprises:
- i. a layer of intestinal interstitial tissue comprising intestinal myofibroblasts;
- and
- ii. a layer of intestinal epithelial cells on in contact with the apical surface of the layer of intestinal interstitial tissue;
- b. determining the viability or functionality of the intestinal tissue model;
- and
- c. assessing the ability of the candidate therapeutic agent to reverse or reduce an intestinal disorder or injury based on the determined viability or functionality of the intestinal tissue model compared to a control intestinal tissue model that has not been contacted with the candidate therapeutic agent.
A method of assessing the effect of a potential toxic agent on intestinal function, the method comprising:
- a. contacting a bioprinted intestinal tissue model with the potential toxic agent, wherein the intestinal tissue model comprises:
- i. a layer of intestinal interstitial tissue comprising intestinal myofibroblasts;
- and
- ii. a layer of intestinal epithelial cells in contact with the apical surface of the layer of intestinal interstitial tissue;
- b. measuring the effect of the potential toxic agent on the viability or functionality of the intestinal tissue model.
A method of predicting the effective dosing concentration and dosing schedule of a candidate therapeutic agent, the method comprising:
- a. contacting a bioprinted intestinal tissue model with varying concentrations or amounts of the candidate therapeutic agent, wherein the intestinal tissue model comprises:
- i. a layer of intestinal interstitial tissue comprising intestinal myofibroblasts;
- and
- ii. a layer of intestinal epithelial cells in contact with the apical surface of the layer of intestinal interstitial tissue;
- b. measuring the effect of the agent on the viability or functionality of the intestinal tissue model over time;
- and
- c. measuring the recovery of the intestinal tissue model over time to determine the minimum timing between doses that provide efficacy.
A method of assessing the ability of a potential toxic agent to induce an intestinal disorder or injury, the method comprising:
- a. contacting a bioprinted intestinal tissue model with the potential toxic agent, wherein the intestinal tissue model comprises:
- i. a layer of intestinal interstitial tissue comprising intestinal myofibroblasts;
- and
- ii. a layer of intestinal epithelial cells on in contact with the apical surface of the layer of intestinal interstitial tissue;
- b. determining the viability or functionality of the intestinal tissue model;
- and
- c. assessing the ability of the potential toxic agent to induce an intestinal disorder or injury based on the determined viability or functionality of the intestinal tissue model compared to a control intestinal tissue model that has not been contacted with the potential toxic agent.
A method of assessing the ability of a candidate therapeutic agent to reduce or prevent an intestinal disorder or injury, the method comprising:
- a. contacting a bioprinted intestinal tissue model with the candidate therapeutic agent, wherein the intestinal tissue model comprises:
- i. a layer of intestinal interstitial tissue comprising intestinal myofibroblasts;
- and
- ii. a layer of intestinal epithelial cells on the layer of intestinal interstitial tissue;
- b. contacting the intestinal tissue model with a treatment, compound, or infectious agent that is capable of giving rise to a phenotype of an intestinal disorder or injury in the intestinal tissue model;
- c. determining the viability or functionality of the intestinal tissue model;
- and
- d. assessing the ability of the candidate therapeutic agent to reduce or prevent an intestinal disorder or injury based on the determined viability or functionality of the intestinal tissue model compared to a control intestinal tissue model that has not been contacted with the candidate therapeutic agent.
Dependencies are inferred from the claim text.