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