Granted Patent B2

US 10,500,230 · App. 11/871,045 · Granted Dec 10, 2019

Inventors: David C. Colter (Hamilton, NJ); Agnieszka Seyda (Franklin Park, NJ); Charito S. Buensuceso (North Brunswick, NJ); Anna Gosiewska (Skillman, NJ)

Assignee: DePuy Synthes Products, Inc.

A61K35/22C12N5/0686C12N5/0687A61K35/12C12N2533/40

Abstract

Claims (20)

1. An implant comprising a thawed human kidney cell population derived from single cell clones, wherein said cell population is capable of self-renewal and expansion in culture, is positive for expression of HLA-I and CD44 and at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5, and is negative for the expression of CD133, E-cadherin, and Wnt-4 and at least one of Sox2, FGF4, hTert, SIX2 or GATA-4; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

2. The implant of claim 1 , wherein the cell population is positive for at least one of cell-surface markers CD24, CD29, CD49c, CD73, CD90, CD166, or SSEA-4, and negative for at least one of cell-surface markers HLA II, CD31, CD34, CD45, CD56, CD80, CD86, CD104, CD105, CD117, CD138, or CD141.

3. The implant of claim 1 , wherein the cells are derived from kidney cortex.

4. An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5 and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 or GATA-4 wherein the cell population secretes at least one of trophic factors FGF2, HGF, TGFα, TIMP-1, TIMP-2, MMP-2 or VEGF and does not secrete at least one of trophic factors PDGF-bb or IL12p70; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

5. The implant of claim 1 , wherein the cell population comprises kidney progenitor cells.

6. An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5 and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 or GATA-4, wherein the cell population comprises kidney progenitor cells, and wherein the kidney progenitor cells are capable of differentiating to adipocytes or osteoblasts; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

7. An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, and EpoR and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 and GATA-4; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

8. An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, and EpoR, negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 and GATA-4; positive for cell-surface markers HLA I, CD24, CD29, CD44, CD49c, CD73, CD90, CD166, and SSEA-4; and negative for cell-surface markers HLA II, CD31, CD34, CD45, CD56, CD80, CD86, CD104, CD105, CD117, CD133, CD138, CD141, and E-cadherin; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

9. An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, EpoR, BMP2, BMP7, and GDF5, and negative for the expression of Sox2, FGF4, and hTert; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

10. The implant of claim 9 , wherein the cell population is positive for cell-surface markers CD24, CD29, CD44, CD49c, CD73, CD90, CD166, and SSEA-4; and negative for cell-surface markers CD31, CD34, CD45, CD56, CD104, CD105, CD117, CD133, CD138, CD141, and E-cadherin.

11. The implant of claim 1 , wherein said biocompatible polymer is synthetic.

12. The implant of claim 11 , wherein said synthetic polymer is selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

13. The implant of claim 11 , wherein said biocompatible synthetic polymer is a polyester.

14. The implant of claim 13 , wherein the polyester is selected from the group consisting of homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

15. The implant of claim 4 , wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

16. The implant of claim 6 , wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

17. The implant of claim 7 , wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

18. The implant of claim 8 , wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

19. The implant of claim 9 , wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

20. The implant of claim 1 , wherein the cells form a monolayer on the matrix.

Assignments (9)