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 assessing whether a kidney disease (KD) patient, comprising chronic kidney failure, is responsive to treatment with a therapeutic comprising an enriched population of renal cells, the method comprising:
detecting amount of a miRNA biomarker comprised in vesicles in a test urine sample obtained from a KD patient treated with the therapeutic, as compared to or relative to the amount of the miRNA biomarker comprised in vesicles in a control urine sample,
wherein a higher amount of the miRNA biomarker comprised in vesicles in the test urine sample as compared to the control urine sample is indicative of the patient's responsiveness to treatment with the therapeutic,
wherein the enriched population of renal cells is enriched for:
(i) tubular cells, and/or
(ii) erythropoietin-producing, glomerular and vascular cells; and
wherein the miRNA biomarker comprises one or more of: miR-22, miR-124, miR-15b, miR-143, let-7a, miR-21, miR-194, miR-130a, miR-23b, miR-30d, miR-429, miR-141, miR-200c, miR-30b-5p, miR-200a, miR-30c, miR-30a, miR-30d*, miR-30e, miR30a*, miR-151, miR-30e*, miR-146a, miR-10a-3p, and miR-449a.
2. The method of claim 1 , wherein the enriched population of renal cells is enriched for tubular cells, and wherein the enriched population of renal cells further comprises epithelial cells of the collecting duct system.
3. The method of claim 1 , wherein the miRNA comprises one or more of miR-30b-5p, miR-449a, miR-146a, miR-130a, miR-23b, miR-21, miR-124, miR-151, miR-30c, miR-15b, miR-30a*, miR-30d, miR-30e*, miR-429, miR-30d*, miR-141, miR-200a, miR-30a, miR-30e, miR-200c, or miR-429.
4. The method of claim 1 , wherein the miRNA comprises one or more of miR-30b-5p, miR-449a, miR-146a, miR-130a, miR-23b, miR-21, miR-124, or miR-151.
5. The method of claim 1 , wherein the miRNA comprises one or more of miR-21, miR-30c, or miR-23b.
6. The method of claim 1 , wherein the miRNA comprises one or more of miR-146a, miR-130a, or miR-23b.
7. The method of claim 1 , wherein the miRNA comprises one or more of miR-15b, miR-30a*, miR-30d, miR-30e*, miR-151, miR-429, miR-21, miR-30b-5p, miR-30d*, miR-141, miR-200a, miR-30a, miR-30c, miR-30e, miR-146a, or miR-200c.
8. The method of claim 5 , wherein the miRNA comprises one or more of miR-30b-5p, miR-429, or miR-200a.
9. The method of claim 1 , wherein the vesicles comprise microvesicles.
10. The method of claim 2 , wherein the therapeutic further comprises a second enriched population of renal cells,
wherein the second enriched population of renal cells is enriched for erythropoietin-producing, glomerular and vascular cells.
11. The method of claim 1 , wherein the chronic kidney failure is secondary to diabetes.
12. The method of claim 1 , wherein the chronic kidney failure is secondary to hypertension.
13. The method of claim 1 , wherein the control urine sample is obtained from the KD patient prior to treatment with the therapeutic.
14. The method of claim 1 , further comprising assessing the KD patient as responsive to treatment with the therapeutic if the miRNA biomarker comprised in vesicles in the test urine sample as compared to the control urine sample is in the higher amount.
15. The method of claim 14 , wherein the enriched population of renal cells is enriched for renal tubular cells.
16. The method of claim 15 , wherein the enriched population of renal cells further comprises epithelial cells of the collecting duct system.
17. The method of claim 14 , wherein the control urine sample is obtained from the KD patient prior to treatment with the therapeutic.
18. The method of claim 8 , wherein the control urine sample is obtained from the KD patient prior to treatment with the therapeutic.