Macrophage Cell Therapy to Treat Orthopedic Injury

Abstract

An ex vivo generated population of tissue-specific alternatively-activated macrophages and methods of making and using such macrophages for treating orthopedic injury are provided.

1 . A method of treatment to alleviate disease or injury associated with an orthopedic injury in a subject in need thereof, the method comprising the step of:
 administering to the subject a population of cells selected from tendon exosome educated macrophages (tendon-EEM).   
     
     
         2 . The method of  claim 1 , wherein the tendon-EEM in the population are eotaxin low, TGF-α low, and IL-13 low. 
     
     
         3 . The method of  claim 1 , wherein the population of cells is administered by injection. 
     
     
         4 . The method of  claim 3 , wherein the population of cells is administered by injection with a pharmaceutically acceptable carrier. 
     
     
         5 . The method of  claim 1 , wherein the population of cells is administered surgically. 
     
     
         6 . The method of  claim 1 , wherein the orthopedic injury is selected from the group consisting of a partial tendon tear, a complete tendon tear, a partial tendon laceration, a complete tendon laceration, a partial tendon avulsion, a complete tendon avulsion, a partial ligament tear, a complete ligament tear, a partial ligament laceration, a complete ligament laceration, tendinopathy, tendinosis, tendinitis, meniscal tears, joint capsule tears. 
     
     
         7 . The method of  claim 1 , wherein the orthopedic injury is selected from the group consisting of plantar fasciitis, tennis elbow, bicep tendinitis, and carpal tunnel syndrome. 
     
     
         8 . The method of  claim 1 , wherein the orthopedic injury is postsurgical inflammation, angiogenesis, fibrosis, degradation of repaired or replaced tissues as well as peri-ligamentous or peri-tendonous tissues. 
     
     
         9 . The method of  claim 8 , wherein the peri-ligamentous or peri-tendonous tissues comprise cartilage. 
     
     
         10 . A method of treatment to alleviate disease or injury associated with an orthopedic injury in a subject in need thereof, the method comprising the step of:
 obtaining a population of CD14+ cells from the subject by leukapheresis;   co-culturing the population of CD14+ cells with tendon derived mesenchymal stem cells or an extracellular factor derived therefrom in vitro until the population of CD14+ cells acquires an anti-inflammatory macrophage phenotype; and   administering to the subject the population of anti-inflammatory macrophage phenotype cells.   
     
     
         11 . The method of  claim 10 , wherein the extracellular factor is derived from tendon or tendon derived mesenchymal stem cells. 
     
     
         12 . The method of  claim 11 , wherein the extracellular factor comprises exosomes, micro-vesicles, and/or extracellular matrix. 
     
     
         13 . The method of  claim 10 , wherein the population of CD14 +  cells comprises monocytes. 
     
     
         14 . The method of  claim 10 , wherein the subject is first treated with a mobilizing agent prior to leukapheresis. 
     
     
         15 . The method of  claim 14 , wherein the mobilizing agent is selected from the group consisting of G-CSF, GM-CSF, and plerixafor. 
     
     
         16 . A method of treatment to alleviate disease or injury associated with an orthopedic injury in a subject in need thereof, the method comprising the step of:
 obtaining a population of CD14+ cells from the subject by leukapheresis;   co-culturing the population of CD14+ cells with adipose derived mesenchymal stem cells or an extracellular factor derived therefrom in vitro until the population of CD14+ cells acquires an anti-inflammatory macrophage phenotype; and   administering to the subject the population of anti-inflammatory macrophage phenotype cells.   
     
     
         17 . The method of  claim 16 , wherein the extracellular factor is derived from adipose or adipose derived mesenchymal stem cells. 
     
     
         18 . The method of  claim 17 , wherein the extracellular factor comprises exosomes, micro-vesicles, and/or extracellular matrix. 
     
     
         19 . The method of  claim 16 , wherein the population of CD14 +  cells comprises monocytes. 
     
     
         20 . The method of  claim 16 , wherein the subject is first treated with a mobilizing agent prior to leukapheresis. 
     
     
         21 . The method of  claim 20 , wherein the mobilizing agent is selected from the group consisting of G-CSF, GM-CSF, and plerixafor.