Selective cell therapy for the treatment of renal failure

• US 9,534,203 B2
• Filed: 09/16/2015
• Issued: 01/03/2017
• 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:
  US14/856,043
• Publication Number:
  US 20160002603A1
• Time in Patent Office: 475 Days
• Field of Search: 435/325
• 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: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 2500/02 Atmosphere, e.g. low oxygen conditions
• CPC Class Codes: C12N 2502/256 Renal cells
• CPC Class Codes: C12N 5/0686 Kidney cells
• CPC Class Codes: G01N 15/01 specially adapted for biological cells, e.g. blood cells investigating sedimentation of particle suspensions in blood G01N15/05
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: G01N 2015/1028 Sorting particles
• CPC Class Codes: G01N 33/56966 Animal cells

Abstract

Provided herein are isolated populations of kidney cells harvested from differentiated cells of the kidney, wherein cells have been expanded in vitro. The kidney cells may include peritubular interstitial cells of the kidney, and preferably produce erythropoietin (EPO). The kidney cells may also be selected based upon EPO production. Methods of producing an isolated population of EPO producing cells are also provided, and methods of treating a kidney disease resulting in decreased EPO production in a patient in need thereof are provided, including administering the population to the patient, whereby the cells produce EPO in vivo.

Claims

1. A method of producing an isolated population of erythropoietin (EPO) producing cells, said method comprising the steps of:

providing differentiated mammalian kidney cells comprising peritubular interstitial cells;

growing said peritubular interstitial cells in vitro in co-culture with multiple other kidney cell types;

passaging said differentiated mammalian kidney cells in vitro from 2 to 9 times, wherein said peritubular interstitial cells produce EPO after said passaging; and

then,

selecting said differentiated mammalian kidney cells for a subpopulation of cells comprising said peritubular interstitial cells producing EPO, wherein said selecting comprises selection based upon density and size,

thereby producing an isolated population of EPO producing cells,

subject to the proviso that the cells of said population of EPO producing cells are not transfected with an exogenous DNA encoding a polypeptide.

2. The method of claim 1, wherein said passaging step comprises growth of said differentiated mammalian kidney cells in a medium comprising insulin transferrin selenium (ITS).

3. The method of claim 1, wherein said differentiated mammalian kidney cells of said providing step further comprises endothelial cells of the kidney.

4. The method of claim 1, wherein said selecting comprises the use of centrifugal gradients.

5. The method of claim 1, wherein said passaging is carried out from 2 to 5 times.

6. The method of claim 1, wherein said passaging is carried out from 3 to 5 times.

7. The method of claim 1, wherein said population produces EPO without manipulation with an exogenous chemical or exogenous gene that stimulates production of EPO.

8. The method of claim 1, wherein said population produces EPO under normoxic conditions in vitro without manipulation with an exogenous chemical or exogenous gene that stimulates production of EPO.

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

10. The method of claim 1, wherein said growing is carried out under hypoxic conditions.

11. The method of claim 1, wherein said differentiated mammalian kidney cells are positive for GLEPP1 and/or Tamm Horsfall after said passaging.

12. The method of claim 1, said method further comprising

providing the isolated population of EPO producing cells in a pharmaceutically acceptable carrier.

13. The method of claim 12, wherein said pharmaceutically acceptable carrier is suitable for injecting or implanting into a patient.

14. The method of claim 12, wherein said pharmaceutically acceptable carrier comprises a biodegradable scaffold suitable for implanting into a kidney of a patient.

15. The method of claim 12, wherein said pharmaceutically acceptable carrier is a gel.

16. The method of claim 15, wherein the gel is an agar gel, a collagen gel, a fibrin gel, or a hydrogel.

17. The method of claim 13, wherein said cells are autogeneic with respect to the patient.

18. The method of claim 14, wherein said cells are autogeneic with respect to the patient.