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 one or more biocompatible synthetic polymers; and
b) an isolated human renal cell population 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 cell population comprising large granular cells of the collecting duct and tubular system, wherein the B1 cell population has a density of about <1.045 g/ml.
2. The 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 cell population.
3. The construct of claim 1 wherein the biomaterial is configured as a liquid or semi-liquid gel suitable for embedding, attaching, suspending, or coating the cell population.
4. The construct of claim 1 , wherein the biomaterial is comprised of a predominantly high-molecular weight species of hyaluronic acid (HA) in hydrogel form.
5. The construct of claim 1 , wherein the biomaterial is comprised of a predominantly high-molecular weight species of hyaluronic acid in porous foam form.
6. The construct of claim 1 , wherein the biomaterial is comprised of a poly-lactic acid-based foam having pores of between about 50 microns to about 300 microns.
7. The 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.
8. The construct of claim 1 or 7 , wherein the human renal cell population is enriched for renal tubular cells.
9. The construct of claim 1 or 7 , wherein the human renal cell population is enriched for one or more bioactive cell populations.
10. The construct of claim 9 , wherein the one or more bioactive cell populations is obtainable by centrifugation on a density gradient after ex vivo culture.
11. The construct of claim 10 , wherein the one or more bioactive cell population comprises 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.
12. The construct of claim 10 , wherein the one or more bioactive cell population comprises 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.
13. The construct of claim 10 , wherein the one or more bioactive cell population comprises 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.
14. The construct of claim 10 , 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 construct of claim 10 , 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 construct of claim 10 , 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.