Kidney structures and methods of forming the same

• US 9,580,688 B2
• Filed: 11/13/2009
• Issued: 02/28/2017
• 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.
• Primary Examiner(s): Babic, Christopher M
• Assistant Examiner(s): Hiriyanna, Kelaginamane T
• Application Number:
  US12/618,338
• Publication Number:
  US 20100112062A1
• Time in Patent Office: 2,664 Days
• Field of Search: 424/93.7
• US Class Current: 1/1
• 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. A method of treating a kidney disease in a patient in need thereof, said method comprising:

providing a composition comprising an isolated population of differentiated mammalian kidney cells comprising peritubular interstitial cells, wherein said cells are harvested from differentiated cells of a mammalian kidney tissue, passaged in vitro from 2 to 9 times, and seeded onto a three dimensional matrix, wherein (i) the cells of said population produce erythropoietin (EPO) under normoxic conditions, and (ii) the differentiated cells of the mammalian kidney tissue or the population of cells have not been manipulated by the introduction of an exogenous gene that stimulates the production of EPO or by an exogenous chemical that stimulates the production of EPO; and

administering said composition to said patient in an amount effective to treat said kidney disease by surgically implanting said composition subcutaneously or into the kidney of said patient,

to thereby treat said kidney disease in said patient in need thereof.

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

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

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

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

5. The method of claim 1, wherein said cells are human.

6. The method of claim 1, wherein said matrix comprises neutralized collagen type I.

7. The method of claim 1, 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.

8. The method of claim 7, wherein said anemia is an anemia of renal failure.

9. The method of claim 7, wherein said anemia is an anemia of end-stage renal disease.

10. The method of claim 1, wherein the matrix comprises a gel.

11. The method of claim 10, wherein the gel is a hydrogel.

12. The method of claim 10, wherein the gel is solidified.

13. The method of claim 1, wherein at least 40% or more of the cells of said population produce erythropoietin (EPO).

14. The method of claim 1, wherein at least 20% or more of the cells of said population produce erythropoietin (EPO).

15. The method of claim 1, wherein said kidney disease results in decreased EPO production in a patient, and wherein said cells produce EPO in vivo.

16. The method of claim 1, wherein said cells are syngeneic with respect to the patient.

17. The method of claim 1, wherein said cells are autogeneic with respect to the patient.

18. The method of claim 1, wherein the three dimensional matrix is biodegradable, and the population is provided in a treatment-effective amount.

19. The method of claim 1, wherein said differentiated mammalian kidney cells have been passaged in vitro from 2 to 6 times.