Cell populations having immunoregulatory activity, method for isolation and uses

Abstract

The present invention provides a population of connective tissue derived cells that respond to interferon-gamma (IFN-γ) by expressing indolamine-2,3-dioxygenase (IDO) for use in preventing, treating or ameliorating one or more symptoms associated with disorders in which modulation of a subject's immune system is beneficial, including, but not limited to, autoimmune diseases, inflammatory disorders, and immunologically mediated diseases including rejection of transplanted organs and tissues.

1 .- 89 . (canceled) 
     
     
         90 . (canceled) 
     
     
         91 . A method of treating an inflammatory disease in a subject comprising systemically administering to the subject an isolated cell population from connective tissue, wherein the cells of said cell population express indolamine 2,3-dioxygenase (IDO) upon stimulation with interferon-gamma (IFN-γ), wherein the inflammatory disease is inflammatory bowel disease. 
     
     
         92 . The method of  claim 91 , wherein the subject is a human. 
     
     
         93 . The method of  claim 91 , wherein the inflammatory disease is refractory to one or more anti-inflammatory agents, optionally wherein the one or more anti-inflammatory agents are a steroidal anti-inflammatory drug and/or a monoclonal antibody such as Infliximab. 
     
     
         94 . The method of  claim 93 , wherein the inflammatory bowel disease is Crohn's disease. 
     
     
         95 . The method of  claim 91 , wherein the cells of the cell population were obtained from bone marrow. 
     
     
         96 . The method of  claim 91 , wherein the cells of the cell population were obtained from bone marrow by aspiration. 
     
     
         97 . The method of  claim 91 , wherein the cells of the cell population were obtained from adipose tissue. 
     
     
         98 . The method of  claim 91 , wherein the cells of the cell population are human cells. 
     
     
         99 . The method of  claim 91 , wherein the cells are negative for at least one, two, or all of the following surface markers: CD31, CD34 and CD133. 
     
     
         100 . The method of  claim 91 , wherein the cells of said cell population:
 a) do not express markers specific for antigen-presenting cells (APC),   b) do not express IDO constitutively,   c) express IDO upon stimulation with IFN-γ, and   d) present capacity to be differentiated into at least two cell lineages.   
     
     
         101 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises expanding cells ex vivo. 
     
     
         102 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises culturing cells without differentiation on a solid surface in the presence of a suitable culture medium or a suitable serum, and incubating the cells under conditions which allow the cells to adhere to the solid surface and proliferate. 
     
     
         103 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises passaging cells at least two times, or wherein cells are passaged at least 10 times, at least 15 times or at least 20 times. 
     
     
         104 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises passaging cells at least 10 times. 
     
     
         105 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises passaging cells at least 15 times. 
     
     
         106 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises passaging cells at least 20 times. 
     
     
         107 . The method of  claim 103 , wherein the preparation method comprises selecting cells that remain adhered to the solid surface after at least two passages. 
     
     
         108 . The method of  claim 91 , wherein the cells of the cell population were prepared by a preparation method that comprises:
 (i) preparing a cell suspension from a sample of a connective tissue;   (ii) recovering the cells from said cell suspension;   (iii) incubating said cells in a suitable cell culture medium on a solid surface under conditions which allow cells to adhere to the solid surface and proliferate;   (iv) washing said solid surface after incubation to remove non-adhered cells;   (v) selecting the cells which after being passaged at least twice in such medium remain adhered to said solid surface; and   (vi) confirming that the selected cell population presents the phenotype of interest.