Modulation of splenocytes in cell therapy
The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that have one or more of the following effects in an injured subject: interact with splenocytes, preserve splenic mass, increase proliferation of CD4 + and CD8 + T-cells, increase IL-4 and IL-10, decrease IL-6 and IL-1β, and increase M2:M1 macrophage ratio at the site of injury. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to have these effects. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for achieving these effects.
1. A method for determining a therapeutically effective amount of cells administered to a subject, the cells having the ability to (1) preserve splenic mass in an injury, (2) increase splenocyte proliferation in the spleen, or (3) increase T-regulatory cells, the method comprising assaying one or more in vivo biomarkers by performing one or more of (1) an assay of splenic mass in an injury, (2) an assay of splenocyte proliferation in the spleen, and (3) an assay of T-regulatory cells, following administration of the cells to the subject, wherein said cells that are assayed are non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1 or rox-1 and/or can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal germ layers.
2. The method of claim 1 wherein the ability of the cells to preserve splenic mass in an injury is determined by performing an assay of splenic mass in an injury.
3. The method of claim 1 wherein the ability of the cells to increase splenocyte proliferation in the spleen is determined by performing an assay of splenocyte proliferation in the spleen.
4. The method of claim 1 wherein the ability of the cells to increase T-regulatory cells is determined by performing an assay of T-regulatory cells.
5. The method of claim 1 wherein the cells express telomerase.
6. The method of claim 1 wherein the cells express oct4.
7. The method of claim 1 wherein the cells express oct4 and telomerase.
8. The method of claim 1 wherein the cells can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal germ layers.
9. The method of claim 1 wherein the cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers.
10. The method as in any of claims 6 - 7 wherein the cells express oct4 and telomerase and can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.
11. The method as in any of claims 1 - 4 and 5 - 9 wherein the cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers and express telomerase and oct4.
12. The method as in any of claims 1 - 4 and 5 - 9 wherein the cells are human.
13. The method of claim 12 wherein the cells are derived from bone marrow.
14. The method of claim 1 wherein the cells are human.
15. The method of claim 1 , in which the injury is selected from the group consisting of acute and chronic conditions in cardiovascular, e.g., acute myocardial infarction; central nervous system injury, e.g., stroke; peripheral vascular disease; pulmonary, e.g., asthma, ARDS; autoimmune, e.g., rheumatoid arthritis, multiple sclerosis, lupus, sclerodoma; psoriasis; gastrointestinal, e.g., graft-versus-host-disease, Crohn's disease, diabetes, ulcerative colitis, acute and chronic transplantation rejection, dermatitis, colitis, alveolitis, bronchiolitis obliterans, ileitis, pancreatitis, glomerulonephritis, uveitis, arthritis, hepatitis, enteritis, ischemic stroke, multiple sclerosis, Alzheimer's Disease, ALS, Parkinson's Disease, hypoxic-ischemia, neonatal hypoxic ischemia, and traumatic brain or spinal cord injury.