Generation of therapeutic cells using extracellular components of target organs

Abstract

The invention relates to an ex vivo generated population of tissue-specific anti-inflammatory macrophages and methods of making and using such macrophages.

1 - 20 . (canceled) 
     
     
         21 . A method for generating an anti-inflammatory macrophage, the method comprising the step of:
 co-culturing a population of isolated CD14 +  cells with isolated cardiac fibroblast-derived extracellular matrix (CF-ECM) in vitro until the population of isolated CD14 +  cells acquires an anti-inflammatory macrophage phenotype, wherein the population of anti-inflammatory macrophages comprises cardiac fibroblast-derived extracellular matrix educated macrophages (CF-ECM-EM) that express CD163 high, CD206 high, PD-L1 high, CD68 low, HLA-DR low, and CD86 low as compared to uneducated macrophages.   
     
     
         22 . The method of  claim 21 , wherein the cardiac fibroblast is derived from embryonic stem cells or induced pluripotent stem cells. 
     
     
         23 . A population of anti-inflammatory macrophages produced by the method of  claim 21 , the population comprising cardiac fibroblast-derived extracellular matrix educated macrophages (CF-ECM-EM) that express CD163 high, CD206 high, PD-L1 high, CD68 low, HLA-DR low, and CD86 low as compared to uneducated macrophages. 
     
     
         24 . A method of treatment to alleviate a cardiovascular disease in a subject in need thereof, the method comprising administering to the subject the population of macrophages of  claim 23 . 
     
     
         25 . The method of  claim 24 , wherein the population of macrophages is administered by injection. 
     
     
         26 . The method of  claim 25 , wherein the cardiovascular disease is ischemic heart failure. 
     
     
         27 . The method of  claim 24 , wherein the population of macrophages is administered by injection with a pharmaceutically-acceptable carrier. 
     
     
         28 . The method of  claim 27 , wherein the carrier is an injectable CF-ECM. 
     
     
         29 . A composition comprising:
 the population of macrophages of  claim 24 ; and   a pharmaceutically-acceptable carrier.   
     
     
         30 . The composition of  claim 29 , wherein the carrier is liquid, oil, lotion, salve, cream, foam, gel, paste, powder, film, and hydrogel. 
     
     
         31 . The composition of  claim 29 , wherein the carrier is an injectable CF-ECM. 
     
     
         32 . The composition of  claim 31 , wherein the CF-ECM additionally comprises cardiac fibroblast-derived exosomes. 
     
     
         33 . The composition of  claim 31 , wherein the CF-ECM additionally comprises growth factors or cytokines.