Bioactive renal cells
The present invention concerns bioactive renal cells 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 isolated human secreted vesicles produced by a renal cell population enriched for bioactive kidney cells,
wherein the vesicles comprise exosomes or microvesicles comprising a paracrine factor that attenuates Plasminogen Activation Inhibitor-1 (PAI-1) and/or Transforming Growth Factor Beta (TGFβ) signaling,
wherein the vesicles have been isolated from the renal cell population, and
wherein the regenerative effect comprises a reduction in renal fibrosis.
2. The method of claim 1 , wherein the vesicles comprise microvesicles.
3. The method of claim 1 , wherein the vesicles comprise exosomes.
4. The method of claim 1 , wherein the paracrine factor inhibits PAI-1 signaling.
5. The method of claim 1 , wherein the paracrine factor is an miRNA.
6. The method of claim 5 , wherein the miRNA inhibits PAI-1 signaling.
7. The method of claim 1 , wherein the paracrine factor inhibits TGFβ.
8. The method of claim 7 , wherein the paracrine factor is an miRNA that inhibits TGFβ.
9. The method of claim 1 , wherein renal fibrosis is reduced by inhibition of epithelial-to-mesenchymal transition (EMT).
10. The method of claim 1 , wherein the bioactive kidney cells comprise:
(a) tubular cells; or
(b) tubular cells and one or more of glomerular cells and vascular cells.
11. The method of claim 10 , wherein the bioactive cells comprise tubular cells and glomerular cells.
12. The method of claim 10 , wherein the bioactive cells comprise tubular cells and vascular cells.
13. The method of claim 1 , wherein the renal cell population is non-autologous to the native kidney.
14. The method of claim 1 , wherein the renal cell population is autologous to the native kidney.
15. The method of claim 6 , wherein the miRNA comprises microRNA 30b-5p or microRNA 449a.