Ex vivo human lung/immune system model using tissue engineering for studying microbial pathogens with lung tropism
First Claim
1. :
- An engineered tissue system comprising of at least one tissue selected from the group consisting of lung tissue, lymphocytes or combinations thereof and at least one mixed engineered tissue comprising at least two individual engineered tissues, where said engineered tissues are generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation.
1 Assignment
0 Petitions
Accused Products
Abstract
A method for studying scaffold-based tissue engineering approaches in combination with the use of progenitor or stem cells to generate new lung tissue in an in vitro system. The engineered tissue system of this invention is used to monitor lung and immune system exposure of pathogen and/or toxins. The method involves growing engineered lung/immune tissue from progenitor cells in a bioreactor and then exposing the engineered lung/immune tissue to a pathogen and/or toxin. Once exposed, response of the engineered tissue is monitored to determine the effects of exposure to the immune component of the tissue and to lung component of the tissue. This invention also involves development of mixed engineered tissues including a first fully functional engineered tissue such as lung tissue and a second fully functional engineered tissued such as immune tissue from a single animal donor. The mixed systems can include more than two engineered tissues.
-
Citations
20 Claims
-
1. :
- An engineered tissue system comprising of at least one tissue selected from the group consisting of lung tissue, lymphocytes or combinations thereof and at least one mixed engineered tissue comprising at least two individual engineered tissues, where said engineered tissues are generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation.
- View Dependent Claims (2, 3, 4, 6)
-
5. (canceled)
-
7. :
- A method for studying tissue responses comprising the steps of;
isolating stem cells from an animal, differentiating and growing the isolated stem cells on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation to form stable, fully functional individual engineered tissues, constructing a mixed engineered tissue from two or more of the individual engineered tissues, exposing the mixed engineered tissue and its constituent individual engineered tissues to a pathogen, a toxin and/or an environmental stress, and monitoring the response of each tissue to the pathogen, toxin and/or environmental stress. - View Dependent Claims (8)
- A method for studying tissue responses comprising the steps of;
-
9. :
- A method for studying tissue responses comprising the steps of;
isolating stem cells from an animal, differentiating and growing the isolated stem cells on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation to form stable, fully functional individual engineered tissues, constructing a mixed engineered tissue from two or more of the individual engineered tissues, exposing the mixed engineered tissue and its constituent individual engineered tissues to a pathogen and monitoring the response of each tissue to the pathogen. - View Dependent Claims (10)
- A method for studying tissue responses comprising the steps of;
-
11. :
- A method for studying a treatment comprising the steps of;
isolating stem cells from an animal, differentiating and growing the isolated stem cells on a scaffold in a bio-reactor under microgravity conditions sufficient tot allow 3D orientation and structural differentiation to form stable, fully functional individual engineered tissues, constructing a mixed engineered tissue from two or more of the individual engineered tissues, exposing the mixed engineered tissue and its constituent individual engineered tissues to a pathogen, a toxin and/or an environmental stress to form infected tissues, monitoring the response of each infected tissue to the pathogen, toxin and/or environmental stress, exposing the infected tissues to a treatment, and monitoring the response of the tissues to the treatment. - View Dependent Claims (12)
- A method for studying a treatment comprising the steps of;
-
13. :
- A method for monitoring treatments against toxins, infections, dysfunctions or diseases, where the method includes the steps of;
inducing a toxic response, infection, dysfunction and/or a disease in a engineered tissue comprising a plurality of individual engineered tissues and one or more mixed engineered tissue including two or more individual engineered tissues, where the tissues are generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation, administering a treatment under treating conditions and monitoring a response of the model to the treatment, where the treating conditions include treatment concentration, if the treatment is a pharmaceutical, treatment intensity, if the treatment is not a pharmaceutical, exposure time, medium properties or other factors that impact pathogenicity and/or toxicity.
- A method for monitoring treatments against toxins, infections, dysfunctions or diseases, where the method includes the steps of;
-
14. :
- An in vitro grown, engineered lung tissue comprising engineered lung tissues derived from lung resident stem or progenitor cells, which normally function in repair and homeostasis of the lung, generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation, where the engineered tissue is are capable of being utilized an as in vitro engineered mammalian including human lung model for examining pathogensis of pathogen.
-
15. :
- An ex vivo engineering lung tissue comprising immature lung cells isolated adult human stem cells from peripheral blood and grown in a rotary cell culture system that maintains the cells in a 3D orientation, where the cells are capable of differentiation into mature, fully functional lung tissue.
- View Dependent Claims (16, 17)
-
18. :
- An implantable ex vivo grown, mature, fully lung cells, tissues or organoids comprising engineered lung tissues derived from lung resident stem or progenitor cells, which normally function in repair and homeostasis of the lung, generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation.
-
19. :
- A cell population comprising somatic lung progenitor cells capable of support lung tissue development in both in vitro and in vivo models, where the cells can be differentiated into numerous cell types that produce Clara cell protein 10 (CC10), cytokeratin, and surfactant protein C(SP-C) prior to formation of cell/polymer constructs. The present invention also provides long-term (4-8 week) in vitro stable cultures of tissue engineered lung epithelium as human lung models for pathogenesis studies using influenza A virus and/or other pathogens and/or toxins.
-
20. :
- An engineered tissue for producing anti-microbial peptides called defensins and cathelicidins, which are innate immune factors present in airway surface liquid and make up part of the lung'"'"'s natural defenses comprising somatic lung progenitor cells generated on a scaffold in a bio-reactor under microgravity conditions sufficient to allow 3D orientation and structural differentiation to form several different cell types in the lung and respiratory tract including airway epithelial cells, macrophages and neutrophils which produce prostaglandins, cyclooxygenase and lipoxygenase products and de novo metabolism of arachidonic acid to both cyclooxygenase and lipoxygenase products and the production of leukotrienes is dependent on both time in culture and agonist.
Specification