KIDNEY STRUCTURES AND METHODS OF FORMING THE SAME

• US 20100112062A1
• Filed: 11/13/2009
• Published: 05/06/2010
• Est. Priority Date: 06/08/2007
• Status: Active Grant

• Current Assignee: Wake Forest University Health Sciences
• Original Assignee: Wake Forest University Health Sciences
• Inventors: Atala, Anthony, Yoo, James J.
• Granted Patent: US 9,580,688 B2
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/22 Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: C12N 2500/02 Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 5/0686 Kidney cells

Abstract

Provided herein are isolated populations of kidney cells harvested from differentiated cells of the kidney, wherein cells have been expanded in vitro, and methods of use thereof. The cells may be provided in a three dimensional matrix for culturing in vitro and/or implanting in vivo. Methods of seeding cells onto the matrix are also provided.

Claims

1. An isolated population of cells comprising differentiated mammalian kidney cells, wherein said cells are harvested from mammalian kidney tissue, passaged in vitro, and seeded onto a three dimensional matrix.

2. The population of cells according to claim 1, wherein said cells are positive for a marker selected from the group consisting of:

erythropoietin (EPO), neprilysin (NEP), Tamm-Horsfall protein (THP), podocin (POD), and combinations thereof, after said passaging.

3. The population of cells according to claim 1, wherein said population consists essentially of said differentiated mammalian kidney cells.

4. The population of cells according to claim 1, wherein said mammalian kidney cells have been passaged in vitro from 1 to 20 times.

5. The population of cells according to claim 1, wherein said mammalian kidney cells have been passaged in vitro at least 3 times.

6. The population of cells according to claim 1, wherein said mammalian kidney cells have been passaged in vitro from 1 to 5 times.

7. The population of cells according to claim 1, wherein said population has been selected for EPO production prior to having been seeded onto said matrix.

8. The population of cells according to claim 1, subject to the proviso that said cells are not transfected with an exogenous DNA encoding a polypeptide.

9. The population of cells according to claim 1, wherein said cells are human.

10. The population of cells according to claim 1, wherein said matrix comprises neutralized collagen type I.

11. A composition comprising the population of cells according to claim 1 and a pharmaceutically acceptable carrier.

12. A method of treating a kidney disease in a patient in need thereof, said method comprising:

providing a composition comprising the population of cells according to claim 1; and

administering said composition to said patient in an amount effective to treat said kidney disease.

13. The method of claim 12, wherein said administering step is carried out by implanting said composition into said patient.

14. The method of claim 12, wherein said kidney disease is an anemia selected from the group consisting of:

an anemia of renal failure, an anemia of end-stage renal disease, an anemia of a chemotherapy, an anemia of a radiation therapy, an anemia of chronic infection, an anemia of an autoimmune disease, an anemia of rheumatoid arthritis, an anemia of AIDS, an anemia of a malignancy, an anemia of prematurity, an anemia of hypothyroidism, an anemia of malnutrition, and an anemia of a blood disorder.

15. A method of producing a three dimensional seeded matrix of differentiated kidney cells, said method comprising the steps of:

providing differentiated kidney cells; and

passaging said differentiated kidney cells, wherein said cells are positive for a marker selected from the group consisting of;

erythropoietin (EPO), neprilysin (NEP), Tamm-Horsfall protein (THP), podocin (POD), and combinations thereof, after said passaging; and

then

seeding said differentiated kidney cells onto a three dimensional matrix; and

then

solidifying said collagen matrix

to thereby produce said three dimensional seeded matrix.

16. The method of claim 15 further comprising the step of selecting said differentiated kidney cells for EPO production.

17. The method of claim 15, wherein said passaging is carried out from 1 to 20 times.

18. The method of claim 15, wherein said matrix comprises neutralized collagen type I.

19. A method of treating a kidney disease resulting in decreased EPO production in a patient in need thereof, said method comprising:

providing a composition comprising an isolated population of EPO producing cells in a three dimensional matrix; and

administering said composition to said patient, whereby said EPO producing cells produce EPO in vivo.

20. The method of claim 19, wherein said administering step is carried out by implanting said composition into the kidney of said patient.

21. The method of claim 19, subject to the proviso that said EPO producing cells are not transfected with an exogenous DNA encoding a polypeptide.

22. The method of claim 19, wherein said kidney disease is an anemia selected from the group consisting of:

an anemia of renal failure, an anemia of end-stage renal disease, an anemia of a chemotherapy, an anemia of a radiation therapy, an anemia of chronic infection, an anemia of an autoimmune disease, an anemia of rheumatoid arthritis, an anemia of AIDS, an anemia of a malignancy, an anemia of prematurity, an anemia of hypothyroidism, an anemia of malnutrition, and an anemia of a blood disorder.

23. The method of claim 19, wherein said EPO producing cells are human.

24. The method of claim 19, wherein said matrix comprises neutralized collagen type I.