Synthetic blood vessels and uses thereof

Abstract

The present invention provides a synthetic blood vessel and use thereof in drug screening, drug delivery and prognoses of cerebrovascular dysfunction.

1 . A method of identifying an amyloid beta (Aβ) modulator, the method comprising:
 i) providing a synthetic blood vessel, 
 ii) providing an Aβ peptide; 
 iii) providing a test compound; 
 iv) contacting the synthetic blood vessel with the Aβ peptide; 
 v) contacting the synthetic blood vessel with the test compound; and 
 vi) determining the level of Aβ deposition or transport, 
 
       wherein the test compound is an Aβ modulator if it inhibits Aβ deposition or enhances Aβ transport. 
     
     
         2 . The method of  claim 1  further comprising contacting the synthetic blood vessel with a lipoprotein. 
     
     
         3 . The method of  claim 2  wherein the lipoprotein is an apolipoprotein or a high-density lipoprotein (HDL). 
     
     
         4 . The method of  claim 3  wherein the apolipoprotein is an apoE isoform. 
     
     
         5 . The method of  claim 2  wherein the lipoprotein is from an astrocyte, unfractionated plasma or serum. 
     
     
         6 . The method of  claim 1  wherein the Aβ peptide is an Aβ40 peptide or an Aβ42 peptide. 
     
     
         7 . The method of  claim 1  wherein the Aβ peptide is from a neuronal cell. 
     
     
         8 . The method of  claim 1  wherein the test compound is added prior to the addition of the Aβ peptide; simultaneously with the Aβ peptide; or subsequent to the addition of the Aβ peptide. 
     
     
         9 . The method of  claim 1  wherein the synthetic blood vessel is a bipartite vessel, a tripartite vessel, a quadripartite vessel or a pentapartite vessel. 
     
     
         10 . The method of  claim 1  wherein the synthetic blood vessel is coupled to a fluid flow system. 
     
     
         11 . The method of  claim 1  wherein the determining is done by an immunological assay or a microscopy assay. 
     
     
         12 .- 18 . (canceled) 
     
     
         19 . A method of determining whether a compound is suitable for delivery to the brain, comprising:
 i) providing a synthetic blood vessel, wherein the synthetic blood vessel is at least a tripartite vessel;   i) contacting the lumen of the synthetic blood vessel with a test compound;   ii) determining the level of transport of the test compound to the antelumen of the tripartite vessel,   
       wherein the test compound is suitable for delivery to the brain if it is transported to the antelumen of the tripartite vessel. 
     
     
         20 . A synthetic blood vessel kit comprising:
 i) a synthetic blood vessel; and   ii) an amyloid beta (Aβ) peptide, together with instructions for use, wherein the synthetic blood vessel kit optionally further comprises a lipoprotein or a monocytic cell or a combination thereof.   
     
     
         21 . The synthetic blood vessel kit of  claim 20  wherein the synthetic blood vessel is a bipartite vessel, a tripartite vessel, a quadripartite vessel or a pentapartite vessel. 
     
     
         22 . The synthetic blood vessel kit of  claim 20  wherein the synthetic blood vessel can be coupled to a fluid flow system. 
     
     
         23 . The synthetic blood vessel kit of  claim 20  wherein the Aβ peptide is an Aβ40 peptide or an Aβ42 peptide. 
     
     
         24 . The synthetic blood vessel kit of  claim 23  wherein the Aβ40 peptide comprises the sequence set forth in SEQ ID NO: 1. 
     
     
         25 . The synthetic blood vessel kit of  claim 23  wherein the Aβ42 peptide comprises the sequence set forth in SEQ ID NO: 2. 
     
     
         26 . The synthetic blood vessel kit of  claim 20  wherein the Aβ peptide is from a neuronal cell. 
     
     
         27 . The synthetic blood vessel kit of  claim 20  wherein the lipoprotein is an apolipoprotein or a high-density lipoprotein (HDL).