CELL POPULATIONS HAVING IMMUNOREGULATORY ACTIVITY, METHOD FOR ISOLATION AND USES
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.