Bioactive renal cells

• US 10,077,442 B2
• Filed: 05/12/2011
• Issued: 09/18/2018
• Est. Priority Date: 05/12/2010
• Status: Active Grant

• Current Assignee: ProKidney LLC, Telefonaktiebolaget LM Ericsson, Tengion, Inc.
• Original Assignee: InRegen (ProKidney LLC)
• Inventors: Bertram, Timothy A., Ilagan, Roger M., Kelley, Russell W., Presnell, Sharon C., Choudhury, Sumana, Bruce, Andrew T., Genheimer, Christopher W., Cox, Bryan R., Guthrie, Kelly I., Basu, Joydeep, Wallace, Shay M., Werdin, Eric, Knight, Oluwatoyin A., Sangha, Namrata D., Ludlow, John W., Halberstadt, Craig R., Payne, Richard, Robins, Neil F., McCoy, Darell, Jain, Deepak, Jayo, Manuel J., Rivera, Elias A., Spencer, Thomas, Watts, Benjamin
• Primary Examiner(s): Bowman, Amy Hudson
• Application Number:
  US13/697,206
• Publication Number:
  US 20160244751A1
• Time in Patent Office: 2,686 Days
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12N 5/0686 Kidney cells
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The present invention concerns bioactive renal cell populations, renal cell constructs, and methods of making and using the same.

Claims

1. A method of providing a regenerative effect to a native kidney comprising in vivo contacting the native kidney with a composition comprising human secreted vesicles produced by an enriched renal cell population, wherein the vesicles comprise exosomes comprising a secreted paracrine factor that attenuates Plasminogen Activation Inhibitor-1 (PAI-1) signaling and/or Transforming Growth Factor Beta (TGFβ

) signaling, and wherein the regenerative effect is a reduction in renal fibrosis.

2. The method of claim 1, wherein the paracrine factor inhibits Plasminogen Activation Inhibitor-1 (PAI-1).

3. The method of claim 1, wherein the paracrine factor is an miRNA.

4. The method of claim 1, wherein the paracrine factor is an miRNA that inhibits Plasminogen Activation Inhibitor-1 (PAI-1).

5. The method of claim 3, wherein the miRNA is extra-vesicular.

6. The method of claim 1 wherein the products are secreted from a renal cell construct comprising an enriched renal cell population directly seeded on or in a scaffold.

7. The method of claim 6 wherein the scaffold comprises a biocompatible material.

8. The method of claim 7 wherein the biocompatible material is a hydrogel.

9. The method of claim 8 wherein the hydrogel is gelatin.

10. The method of claim 1 wherein the regenerative effect is a reduction in epithelial-mesenchymal transition (EMT).

11. The method of claim 1 wherein the population comprises a first cell population, B2, comprising an enriched population of tubular cells having a density between about 1.045 g/mL and about 1.052 g/mL.

12. The method of claim 1 wherein the population comprises an admixture of human renal cells comprising a first cell population, B2, and a second cell population, wherein B2 comprises an enriched population of tubular cells having a density between about 1.045 g/mL and about 1.052 g/mL and wherein the second cell population comprises a B4 cell population having a density between about 1.063 g/mL and about 1.091 g/mL or a B3 cell population having a density between about 1.052 g ml and about 1.063 g/ml.

13. The method of claim 12 wherein the second cell population is a B4 cell population having a density between about 1.063 g/mL and about 1.091 g/mL.

14. The method of claim 12 wherein the second cell population is a B3 cell population having a density between about 1.052 g ml and about 1.063 g/ml.

15. The method of claim 13 wherein the admixture further comprises a third cell population, wherein the third cell population comprises a B3 cell population having a density between about 1.052 g ml and about 1.063 g/ml.

16. The method of claim 1 wherein the enriched renal cell population is non-autologous to the native kidney.

17. The method of claim 1 wherein the enriched renal cell population is autologous to the native kidney.