RENAL CELL POPULATIONS AND USES THEREOF
The present invention concerns enriched heterogeneous mammalian renal cell populations characterized by biomarkers, and methods of making and using the same.
1 . An enriched heterogeneous mammalian renal cell population that express the biomarkers GGT-1 and a cytokeratin.
2 . The cell population according to claim 1 wherein the biomarkers are detected by a monoclonal or polyclonal antibody.
3 . The cell population according to claim 1 wherein greater than 18% of the cells express GGT-1.
4 . The cell population according to claim 1 wherein the cytokeratin is selected from CK8, CK18, CK19 and combinations thereof.
5 . The cell population according to claim 4 wherein the level of expression of the cytokeratin is greater than 80%.
6 . The cell population according to claim 1 wherein the cytokeratin is detected by polyclonal antibody.
7 . The cell population according to claim 1 wherein the cell population expresses AQP.
8 . The cell population according to claim 1 wherein less than 40% of the cells express AQP2.
9 . The cell population according to claim 7 wherein the AQP2 is detected by monoclonal antibody.
10 . The cell population according to claim 1 wherein the mammal is human.
11 . A method of identifying a heterogeneous renal cell population suitable for implantation and/oreliciting a regenerative response said method comprising the steps
Isolating cells from a mammalian kidney sample
Exposing said isolated cells to one or more labeled detection moiety, wherein each labeled detection moiety is directed to a different biomarker and is labeled with a different label
Determining the percentage of cells that express each of said different biomarker.
12 . The method of claim 11 wherein the biomarker is selected from AQP1, AQP2, AQP4, Calbindin, Calponin, CD117, CD133, CD146, CD24, CD31 (PECAM-1), CD54 (ICAM-1), CD73, CK18, CK19, CK40 to 67, CK7, CK8, CK8, CK18, CK19, combinations of CK8, CK18 and CK19, Connexin 43, Cubilin, CXCR4 (Fusin), DBA, E-cadherin (CD324), EPO (erythropoeitin), GGT1, GLEPP1 (glomerular epithelial protein 1), Haptoglobulin, Itgb1 (Integrin β1), KIM-1/TIM-1 (kidney injury molecule-1/T-cell immunoglobulin and mucin-containing molecule), MAP-2 (microtubule-associated protein 2), Megalin, N-cadherin, Nephrin, NKCC (Na-K-Cl-cotransporters), OAT-1 (organic anion transporter 1), Osteopontin, Pan-cadherin, PCLP1 (podocalyxin-like 1 molecule), Podocin, SMA (smooth muscle alpha-actin), Synaptopodin, THP (tamm-horsfall protein), Vimentin, αGST-1 (alpha glutathione S-transferase) and combinations thereof.
13 . The method of claim 11 wherein the labeled detection moiety is an antibody.
14 . A method of treating kidney disease in a mammal comprising administering a heterogeneous renal cell population to the patient, wherein the cell population expresses two or more biomarkers selected from the group consisting of GGT-1, AQP2 and a cytokeratin.
15 . A method of treating kidney disease in a mammal comprising administering a heterogeneous renal cell population to the patient, wherein cells within the cell population have levels of expression for GGT-1 and CK18 are greater than 18% and 80%, respectively.
16 . A method of treating kidney disease in a mammal comprising administering a heterogeneous renal cell population to the patient, wherein cells within the cell population express GGT-1, AQP2 and CK18 at levels of expression in Table 12.4.
17 . The method according to claim 15 or 16 wherein the cell population is cultured on a matrix.
18 . The method according to claim 15 or 16 wherein the cell population is suspended in a gelatin-based biomaterial.
19 . The method according to claim 15 or 16 wherein the mammal is human.