Isolated multipotent mesenchymal stem cell from human adult glomeruli (HGL-MSC), a method of preparing thereof and uses thereof in the regenerative medicine of the kidney
The invention relates to an isolated multipotent glomerular mesenchymal stem cell derived from adult human kidney (hGL-MSC), which is characterized by the marker profile CD133 − , CD146 + , CD34 − and CD105 + . A method of preparing the hGL-MSC of the invention form decapsulated glomeruli is also disclosed, as well as the uses of the hGL-MSC of the invention in the regenerative treatment of the kidney, particularly for the treatment of injuries or diseases affecting renal glomeruli.
1. An isolated multipotent gliomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) expanded in vitro over multiple passages, characterised by the markers CD133(negative), CD146(positive), CD34(negative), CD105(positive), CD24(positive), Oct-4(negative), and Pax-2(positive) and further characterised by the ability to differentiate into at least the following cell types: podocytes, endothelial cells and mesangial cells.
2. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further capable of undergoing osteogenic, adipogenic and chondrogenic differentiation.
3. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further characterized as negative for the marker α-SMA.
4. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further characterized as negative for the marker CD45.
5. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further characterized as negative for the marker CD31.
6. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is positive for a surface marker characteristic of mesenchymal stem cells selected from the group consisting of CD29, CD44, CD73, CD90, CD166 or any combination thereof.
7. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further characterized as positive for the markers Nanog and Musashi.
8. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which is further characterized as positive for vimentin and nestin and negative for cytokeratin.
9. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 1 , which constitutively expresses MHC class I antigens and is further characterized as negative for MHC class II antigens.
10. The multipotent glomerular mesenchymal stem cell derived from adult human kidney glomeruli (hGL-MSC) according to claim 9 , which is further characterized as negative for the costimulatory molecules CD80, CD86 and CD40.
11. A pharmaceutical composition comprising the isolated human glomerular mesenchymal stem cell (hGL-MSC) expanded in vitro over multiple passages according to claim 1 and a pharmaceutically acceptable carrier, diluent and/or vehicle.
12. A method for treating a kidney injury or disease in a subject, comprising administering to the subject an effective amount of the isolated expanded multipotent glomerular mesenchymal stem cell derived from human kidney (hGL-MSC) according to claim 1 .
13. A method according to claim 12 , wherein the kidney injury or disease is a renal glomerulus injury or disease.
14. A therapeutic method of kidney regeneration in a subject in need thereof, comprising administering to the subject an effective amount of the isolated expanded multipotent glomerular mesenchymal stem cell derived from human kidney (hGL-MSC) according to claim 1 .
15. A method for treating a kidney injury or disease in a subject, comprising administering to the subject an effective amount of the isolated expanded multipotent glomerular mesenchymal stem cell derived from human kidney (hGL-MSC) according to the pharmaceutical composition according to claim 11 .
16. A therapeutic method of kidney regeneration in a subject in need thereof, comprising administering to the subject an effective amount of the isolated expanded multipotent glomerular mesenchymal stem cells derived from human kidney (hGL-MSC) according to the pharmaceutical composition according to claim 11 .