Methods, systems and compositions for functional in vitro cellular models of mammalian systems

Abstract

The present invention comprises methods, systems and compositions comprising cell culture analog systems, comprising components which optionally comprise biologically functional cells, and the components and systems function similarly to in vivo conditions.

1 . A method for determining the effect of an input variable on a simulated multi-organ system, comprising contacting at least one cell in a cell culture analog system which comprises a plurality of components, wherein a component comprises one or more chambers, chips or regions, and optionally, one or more types of cells; and one or more sensing elements, wherein one or more of the plurality of components is in fluid connection with another component, with an input variable and recording at least one output parameter. 
     
     
         2 . The method of  claim 1 , wherein a step of recording at least one output parameter comprises obtaining information from a sensing element in a component. 
     
     
         3 . The method of  claim 1 , wherein the plurality of components comprises a cardiac-simulating component comprises cardiac cells cultured on one or more microcantilevers. 
     
     
         4 . The method of  claim 3 , wherein the cardiac-simulating component comprises cardiac cells cultured in a pattern on a microelectrode array with embedded microelectrodes. 
     
     
         5 . The method of  claim 1 , wherein the plurality of components comprises a motoneuron component comprises neurons and myotubes forming neuromuscular junctions cultured on microcantilevers. 
     
     
         6 . The method of  claim 5 , wherein the motoneuron component comprises neurons and myotubes forming neuromuscular junctions cultured in a pattern on a microelectrode array with embedded microelectrodes. 
     
     
         7 . The method of  claim 1 , wherein the plurality of components comprises a cardiac-simulating component and a motoneuron component. 
     
     
         8 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein a cell culture analog system comprises at least a first component comprising a microscale chamber containing a first type of cell under conditions where the first type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the first chamber comprises a first inlet and a first outlet for flow of culture medium; and comprises, a second component comprising a microscale chamber containing a second type of cell under conditions where the second type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the second chamber comprises a second inlet and a second outlet for flow of culture medium; and a microfluidic channel interconnecting the first and second chambers. 
     
     
         13 . The method of  claim 1 , wherein at least one component comprises a first chamber comprising a first cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in vivo; a second component comprises a second chamber of the same or different geometry than the first chamber comprising a second cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in vivo; wherein the first and second chambers are interconnected by fluidic channels; and an inlet and outlet for re-circulation of culture medium. 
     
     
         14 . The method of  claim 1 , wherein the cell culture analog system further comprises serum-free culture medium. 
     
     
         15 . The method of  claim 1 , wherein at least one of the components comprises ex plant tissue from a body. 
     
     
         16 - 21 . (canceled) 
     
     
         22 . A cell culture analog system of  claim 1 , comprising a plurality of components, wherein a component comprises one or more chambers, chips or regions, and one or more types of cells; and one or more sensing elements, wherein one or more of the plurality of components is in fluid connection with another component. 
     
     
         23 . (canceled) 
     
     
         24 . The system of  claim 22 , wherein at least one component is a microfluidic device. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The system of  claim 22 , wherein at least one component comprises a chip comprising biological cells on a microelectrode array comprising surface embedded microelectrodes. 
     
     
         28 . The system of  claim 22 , wherein at least one component comprises at least a first microscale chamber containing a first type of cell under conditions where the first type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in viva, wherein the first chamber comprises a first inlet and a first outlet for flow of culture medium; and optionally comprises, a second component comprising a second microscale chamber containing a second type of cell under conditions where the second type of cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in viva, wherein the second chamber comprises a second inlet and a second outlet for flow of culture medium; and a microfluidic channel interconnecting the first and second chambers. 
     
     
         29 . The system of  claim 22 , wherein at least one component comprises a first chamber comprising a first cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in viva; and a second component comprising a second chamber of the same or different geometry than the first chamber comprising a second cell type maintained under conditions providing at least one pharmacokinetic parameter value comparable to values obtained for the cells in viva; wherein the first and second chambers are interconnected by fluidic channels; and an inlet and outlet for re-circulation of culture medium. 
     
     
         30 . The system of  claim 22 , further comprising one or more additional microscale chambers containing the same or different types of cells as in the first or optionally second chambers, under conditions where the additional cell provides at least one pharmacokinetic parameter value comparable to a value obtained for the same type of cell in vivo, wherein the one or more additional chambers comprise an inlet and outlet for flow of culture medium. 
     
     
         31 - 34 . (canceled) 
     
     
         35 . The system of  claim 22 , wherein the plurality of components are fabricated on the same chip. 
     
     
         36 . The system of  claim 22 , wherein the plurality of components comprise a separate chamber for each organ system. 
     
     
         37 . The system of  claim 22 , wherein the plurality of components comprise components that are fabricated on the same chip and components that comprise a separate chamber for each organ system.