Implantable cellular therapy device for treatment of graft versus host disease and tolerance induction

Abstract

Implantable devices comprising a scaffold, cells, and/or therapeutic molecules are provided. Uses include inhibition of pathological immunity, elaboration of therapeutic growth factors, and immune augmentation. The implantable device may contain a porous substrate structure to which therapeutic cells are adherent, which can be implanted and explanted from a patient. In another embodiment, a medical device includes a porous substrate seeded with therapeutic cells, said device comprising of an additional layer allowing free exchange of molecules without cell escape. Said medical device is seeded with thymic medullary epithelial cells or progenitors of said thymic medullary epithelial cells. In conditions where tolerance to alloreactive donor cells is desired, the thymic medullary epithelial cells or progenitors thereof are derived from recipient cells. In conditions where tolerance to alloreactive recipient cells is desired, the thymic medullary epithelial cells or progenitors thereof are derived from donor cells.

What is claimed is: 
     
         1 . A method of treating an inflammatory condition comprising:
 selecting a population of cells producing soluble anti-inflammatory mediators;   culturing said cells producing soluble anti-inflammatory mediators with a matrix in vitro so as to allow adherence of said cells to said matrix;   overlaying a material with selective permeability over said cells and said matrix so as to allow for diffusion of soluble factors through said material but not escape of cells; and   implanting said enclosed matrix containing therapeutic cells into a patient in need.   
     
     
         2 . The method of  claim 1 , wherein said inflammatory condition is characterized by elevated levels of inflammatory mediators, said mediators selected from the group consisting of: IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, IL-15, IL-17, IL-18, IL-21, IL-23, TNF-alpha, Interferon-gamma, and TRANCE. 
     
     
         3 . The method of  claim 1 , wherein said inflammatory condition is selected from a group comprising of: autoimmunity, transplant rejection, and aging. 
     
     
         4 . The method of  claim 1 , wherein said population of cells producing soluble anti-inflammatory mediators are selected from the group consisting of immature dendritic cells, lymphoid dendritic cells, alternatively activated macrophages, bone marrow mononuclear cells, mesenchymal stem cells, T regulatory cells, NKT cells, hematopoietic stem cells, cord matrix mononuclear cells, adipose tissue mononuclear cells, placental matrix mononuclear cells, cord blood mononuclear cells, and CD5 positive B cells. 
     
     
         5 . The method of  claim 1 , wherein said cell populations are autologous, allogeneic, or xenogeneic. 
     
     
         6 . The method of  claim 1 , wherein said cells are derived from one or a plurality of cell lines. 
     
     
         7 . The method of  claim 1 , wherein said enclosed matrix containing therapeutic cells is administered subcutaneously in a manner allowing for subsequent explantation. 
     
     
         8 . A method of modifying an immune response comprising:
 selecting a population of cells producing soluble immune modulators;   culturing said cells producing soluble immune modulators with a matrix in vitro so as to allow adherence of said cells to said matrix;   overlaying a material with selective permeability over said cells and said matrix so as to allow for diffusion of soluble factors through said material but not escape of cells; and   implanting said enclosed matrix containing therapeutic cells into a patient in need.   
     
     
         9 . The method of  claim 8 , wherein the immune response is an antibody mediated immune response or a cell mediated immune response.