Method of characterizing potential therapeutics by determining cell-cell interactions

Abstract

A method quantitatively analyzes images of two different cell types that interact in producing and maintaining a disease state or other biological condition. The two separate cell types are exposed to an agent or stimulus suspected of influencing the biological condition (e.g., the agent might be a potential therapeutic for treating a cancer). The two different cell types are co-cultured or otherwise allowed to interact with one another before and during exposure to the agent. The images of the cells show how the agent affects the cells' phenotypes, including their viability, migration patterns, etc. The method generates a quantitative phenotype for each cell type by quantitatively analyzing the cell images via an automatic procedure. The quantitative phenotypes typically take the form of a group of scalar or vector descriptors that together provide a “fingerprint.” The descriptors may be size values, positions, morphological values, intensity distributions, etc.

1 . A method of evaluating the effect of interactions between distinct cell types, the method comprising: 
 (a) providing a first cell culture of a first cell type and a second cell culture of a second cell type in a microenvironment in which the cells of the first and second cell cultures share a common medium, and wherein the first and second cell types interact in the common medium and further wherein the first and second cell types interact as part of a biological condition;    (b) imaging the first and second cell types after exposure to an agent or stimulus; and    (c) quantitatively evaluating one or more images obtained in (b) to generate quantitative phenotypic representations of the cells; and    (d) identifying any effects of the agent on the cells in the first and second cell cultures by comparing said quantitative phenotypic representations generated in (c) with phenotypic representations of one or more reference cells, which effects are mediated by interactions between the first and second cell cultures,    wherein the biological condition is an auto-immune disease, neurodegenerative disease, Parkinson's disease, Alzheimer's disease, Type II diabetes, or cardiac disease.    
     
     
         2 . The method of  claim 1 , wherein quantitatively evaluating one of more images identifies at least one of the a change in migration pattern, growth rate, endocytosis, cell shape, and extracellular matrix deposition of the cells of at least one of the first and second cell cultures.  
     
     
         3 . The method of  claim 1 , wherein the agent is a chemical compound or a biological material.  
     
     
         4 . The method of  claim 1 , wherein the agent is a drug candidate.  
     
     
         5 . The method of  claim 1 , wherein the agent is electromagnetic radiation, particle radiation, a non-ambient temperature, a non-ambient pressure, acoustic energy, a mechanical force, an electrical field, a magnetic field, and combinations thereof.  
     
     
         6 - 11 . (canceled)  
     
     
         12 . The method of  claim 1 , wherein the biological condition is an auto-immune disease, and wherein the first cell type is an immune system cell type and the second cell type is a different cell type that is attacked by cells of the first cell type in an auto-immune disease.  
     
     
         13 . The method of  claim 1 , wherein the biological condition is a neurodegenerative disease, and wherein the first cell is a neuron cell type and the second cell type is a neuroglial cell type.  
     
     
         14 . The method of  claim 13 , wherein the biological condition is Parkinson's disease, and wherein the first cell type is a neuron cell type and the second ell type is an astrocyte cell type, oligodendricyte cell type, immune system cell type, or vascular cell type.  
     
     
         15 . The method of  claim 13 , wherein the biological condition is Alzheimer's disease, and wherein the first cell type is a cholinergic neuron cell type and the second cell type is a neuroglial cell type.  
     
     
         16 . The method of  claim 1 , wherein the biological condition is Type II diabetes, and wherein the first cell type is a muscle cell type and the second cell type is an adipocyte cell type, an immune cell type, or a vascular cell type.  
     
     
         17 . The method of  claim 1 , wherein the biological condition is cardiac disease, and wherein the first cell type is a cardiac myocyte and the second cell type is a stem cell, primary cell, fibroblast or endothelial cell of cardiac origin.  
     
     
         18 . The method of  claim 1 , wherein identifying any effects of the agents comprises determining a cell killing potency of the agent.  
     
     
         19 . (canceled)  
     
     
         20 . The method of  claim 1 , wherein the common medium is a cell growth medium or a cell support medium.  
     
     
         21 . The method of  claim 1 , further comprising: 
 prior to imaging, allowing the cells of the first and second cell types to grow in the common growth medium.    
     
     
         22 . The method of  claim 1 , wherein the microenvironment comprises 
 a first compartment in which the first cell culture is grown, and    a second compartment in which the second cell culture is grown, and    wherein the common medium contacts the first and second compartments and the first and second cell cultures.    
     
     
         23 . The method of  claim 22 , wherein the first compartment is a base compartment holding the first cell culture at first level, 
 wherein the second compartment is provided as an insert to the base compartment, and    wherein the second compartment holds the second cell culture at a second level, that is above the first level.    
     
     
         24 - 45 . (canceled)