Isolated renal cells and uses thereof
The invention is directed to isolated renal cells, including tubular and erythropoietin (EPO)-producing kidney cell populations, and methods of isolating and culturing the same, as well as methods of treating a subject in need with the cell populations.
1. An implantable construct for providing improved kidney function to a subject in need comprising: a) a biomaterial comprising a hydrogel, wherein the hydrogel comprises gelatin; and b) an admixture of mammalian renal cells comprising a first renal cell population, B2, comprising an enriched population of tubular cells and having a density between about 1.045 g/mL and about 1.052 g/mL, coated with, deposited on or in, entrapped in, suspended in, embedded in and/or otherwise combined with the biomaterial; wherein the human renal cell population is depleted of a B1 renal cell population comprising large granular cells of the collecting duct and tubular system, wherein the B1 renal cell population has a density of about <1.045 g/ml.
2. The implantable construct of claim 1 , wherein the admixture of mammalian renal cells further comprises a second cell population, B4, comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.063 g/ml and about 1.091 g/ml.
3. The implantable construct of claim 1 , wherein the admixture of mammalian renal cells further comprises a second cell population, B3, comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.052 g/ml and about 1.063 g/ml.
4. The implantable construct of claim 1 , wherein the admixture is derived from mammalian kidney tissue or cultured kidney cells.
5. The implantable construct of claim 1 , wherein the biomaterial is configured as a three-dimensional (3-D) porous biomaterial suitable for entrapment and/or attachment of the admixture.
6. The implantable construct of claim 1 , wherein the biomaterial is configured as a liquid or semi-liquid gel suitable for embedding, attaching, suspending, or coating mammalian cells.
7. The implantable construct of claim 1 , wherein the gelatin is in the form of gelatin microcarrier beads.
8. The implantable construct of claim 1 , wherein the cell population is derived from an autologous kidney sample.
9. The implantable construct of claim 8 , wherein the sample is a kidney biopsy.
10. The implantable construct of claim 1 , wherein the cell population is derived from a non-autologous kidney sample.
11. The implantable construct of claim 1 , wherein the improved kidney function is glomerlo-tubulo-interstial regeneration.
12. The implantable construct of claim 1 , wherein the human renal cell population is further depleted of a B5 cell population comprising debris and small cells of low granularity and viability, wherein the B5 cell population has a density of about >1.091 g/ml.
13. The implantable construct of claim 1 , wherein the one or more bioactive cell populations is obtainable by centrifugation on a density gradient after ex vivo culture.
14. The implantable construct of claim 1 , wherein the one or more bioactive cell population comprises
(a) a B2 cell population comprising an enriched population of tubular cells and having a density between about 1.045 g/mL and about 1.052 g/mL;
(b) a B3 cell population comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.052 g/ml and about 1.063 g/ml; and
(c) a B4 cell population comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.063 g/ml and about 1.091 g/ml.
15. The implantable construct of claim 1 , wherein the one or more bioactive cell
population comprises
(a) a B2 cell population comprising an enriched population of tubular cells and having a density between about 1.045 g/mL and about 1.052 g/mL; and
(b) a B3 cell population comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.052 g/ml and about 1.063 g/ml.
16. The implantable construct of claim 1 , wherein the one or more bioactive cell population comprises
(a) a B2 cell population comprising an enriched population of tubular cells and having a density between about 1.045 g/mL and about 1.052 g/mL; and
(b) a B4 cell population comprising erythropoietin (EPO)-producing cells, glomerular cells and vascular cells and having a density between about 1.063 g/ml and about 1.091 g/ml.
17. The implantable construct of claim 1 , wherein the improved kidney function comprises improved integrity of glomerular filtration mechanisms.
18. The implantable construct of claim 1 , wherein the improved kidney function comprises reduced glomerlo-tubulo-interstial fibrosis and reduced protein loss.