Multilineage-differentiating stress enduring (MUSE) cells for treatment of chronic kidney disease
View Patent ↗An object of the present invention is to provide a novel medical application to regenerative medicine that uses pluripotent stem cells (Muse cells). The present invention provides a cell preparation for treating chronic kidney disease that contains SSEA-3-positive pluripotent stem cells isolated from mesenchymal tissue in the body or cultured mesenchymal cells. The cell preparation of the present invention is based on a renal tissue regeneration mechanism by which Muse cells are made to selectively accumulate at a site of kidney disease and differentiate into cells that compose the kidney by administering Muse cells intravenously to a subject having the aforementioned disease.
1. A method for treating chronic kidney disease in a mammalian subject having damaged renal tissue, the method comprising: administering a cell preparation comprising an effective amount of human pluripotent stem cells positive for SSEA-3 isolated from biological mesenchymal tissue or cultured mesenchymal cells, wherein the human pluripotent stem cells have been concentrated, said human pluripotent stem cells having a plurality of properties, said plurality of properties comprising:
(i) CD105-positively;
(ii) low or absent telomerase activity;
(iii) ability to differentiate into any of the three germ layers;
(iv) absence of demonstration of neoplastic proliferation; and
(v) self-renewal ability;
wherein the human pluripotent stem cells migrate to and accumulate in the damaged renal tissue, wherein upon accumulation said human pluripotent stem cells differentiate into cells constituting renal tissue to thereby treat the chronic kidney disease, wherein the chronic kidney disease is treated on the basis of repression of progression of the chronic kidney disease and improvement of kidney function by means of a renal tissue regeneration mechanism, wherein the chronic kidney disease is selected from the group consisting of chronic glomerular nephritis, renal sclerosis, diabetic nephropathy, renal cyst, chronic pyelonephritis, rapidly progressive glomerulonephritis, malignant hypertension, SLE nephritis, renal amyloidosis, renal/urinary tract tumors, myeloma, obstructive uropathy, renal gout, renal hypoplasia and renal/urinary tract tuberculosis.
2. The method according to claim 1 , wherein the human pluripotent stem cells positive for SSEA-3 contain a concentrated cell fraction as a result of stimulation by external stress.
3. The method according to claim 1 , wherein the human pluripotent stem cells are CD117-negative and CD146-negative.
4. The method according to claim 1 , wherein the human pluripotent stem cells are CD117-negative, CD146-negative, NG2-negative, CD34-negative, vWF-negative and CD271-negative.
5. The method according to claim 1 , wherein the human pluripotent stem cells are CD34-negative, CD117-negative, CD146-negative, CD271-negative, NG2-negative, vWF-negative, Sox10-negative, Snail-negative, Slug-negative, Tyrp1-negative and Dct-negative.
6. The method according to claim 1 , wherein the human pluripotent stem cells have the ability to differentiate into one or more cells selected from the group consisting of foot cells, mesangium cells, glomerular endothelial cells, juxtaglomerular cell, proximal tubular cells, distal tubular cells, vascular endothelial cells, Henle's loop, and collecting tubule cells.
7. The method according to claim 1 , wherein the chronic kidney disease of a kidney having a damaged glomerulus is treated on the basis of prevention of progression of glomerular sclerosis and promotion of reconstruction and repair of the glomerulus.