CAMKK1 AS A NOVEL REGENERATIVE THERAPEUTIC
Disclosed herein are methods of treating an ischemic or inflammatory condition in an organ or tissue of a patient comprising inducing an increase of the level of CAMKK1 in said organ or tissue.
1 . A method of treating an ischemic or inflammatory condition in an organ or tissue of a patient, comprising administering to the patient:
(a) cells comprising: a vector comprising a nucleic acid encoding human calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1) selected from the group of: the protein of SEQ ID NO: 4, the T108A mutant CAMKK1, the S459A mutant CAMKK1, or the T108A/S459A mutant CAMKK1, wherein T108 corresponds to position 108 of SEQ ID NO: 2 and 5459 corresponds to position 458 of SEQ ID NO: 2, to said organ or tissue; or
(b) conditioned media from a culture of the cells of (a) that have been modified to have an increase of the level of human CAMKK1 protein to said organ or tissue, thereby preventing fibrosis or increasing vascular density in the organ or tissue of the patient.
2 . The method of claim 1 , wherein said organ or tissue is heart, liver, kidney, brain, spine, lungs, small intestine, large intestine, arteries, joints, cartilage, skin, or any combination thereof.
3 . The method of claim 2 , wherein said organ or tissue is the heart or myocardium.
4 . The method of claim 1 , wherein the vector is a plasmid or a viral vector.
5 . The method of claim 1 , wherein the cells or conditioned media are administered systemically, directly into the ischemic or inflamed tissue, or about the periphery of the ischemic or inflamed tissue.
6 . The method of claim 1 , wherein the cells are mesenchymal stem cells.
7 . The method of claim 1 , wherein the ischemic or inflammatory condition is acute myocardial infarction, heart failure, peripheral artery disease, stroke, liver disease, ischemic kidney disease, multiple sclerosis, traumatic brain injury, spinal cord injury, graft versus host disease (GVHD), diabetes, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, an injury from a solid organ transplant, an orthopedic injury, a cartilage disorder, a wound, or any combination thereof.
8 . The method of claim 1 , further comprising administering one or more additional regenerative therapies.
9 . The method of claim 8 , wherein the one or more regenerative therapies are mesenchymal stem cells derived from bone marrow, adipose tissue, placental tissue, umbilical cord, Wharton's Jelly, menstrual blood, stem cells, M2 macrophages, monocytes, or any combination thereof.
10 . The method of claim 9 , wherein the stem cells are neural progenitor cells, endothelial progenitor cells, organ specific endogenous stem cells, or any combination thereof.
11 . The method of claim 10 , wherein the organ specific endogenous stem cells are cardiac ckit+ cells.