Selective cell therapy for the treatment of renal failure

Abstract

Provided herein are isolated populations of kidney cells harvested from differentiated cells of the kidney, wherein cells have been expanded in vitro. The kidney cells may include peritubular interstitial cells of the kidney, and preferably produce erythropoietin (EPO). The kidney cells may also be selected based upon EPO production. Methods of producing an isolated population of EPO producing cells are also provided, and methods of treating a kidney disease resulting in decreased EPO production in a patient in need thereof are provided, including administering the population to the patient, whereby the cells produce EPO in vivo.

1 . An isolated population of cells comprising differentiated peritubular interstitial cells harvested from kidney tissue and passaged in vitro. 
   
   
       2 . The population of cells according to  claim 1 , wherein said differentiated peritubular interstitial cells produce erythropoietin (EPO). 
   
   
       3 . The population of cells according to  claim 1 , wherein said population consists essentially of differentiated peritubular interstitial cells. 
   
   
       4 . The population of cells according to  claim 1 , wherein said population has been passaged from 1 to 4 times. 
   
   
       5 . The population of cells according to  claim 1 , wherein said population has been selected for EPO production. 
   
   
       6 . The population of cells according to  claim 1 , subject to the proviso that said cells are not transfected with an exogenous DNA encoding a polypeptide. 
   
   
       7 . A composition comprising the population of cells according to  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       8 . A method of producing an isolated population of EPO producing cells, said method comprising the steps of:
 providing differentiated kidney cells; and   passaging said differentiated kidney cells, wherein said cells produce EPO after said passaging;   thereby producing an isolated population of EPO producing cells.   
   
   
       9 . The method of  claim 8  further comprising the step of selecting said differentiated kidney cells for EPO production. 
   
   
       10 . The method of  claim 8 , wherein said passaging step comprises growth of differentiated kidney cells in a medium comprising insulin transferrin selenium (ITS). 
   
   
       11 . The method of  claim 8 , wherein said differentiated kidney cells of said providing step consists essentially of differentiated peritubular interstitial cells. 
   
   
       12 . The method of  claim 8 , subject to the proviso that said population of EPO producing cells are not transfected with an exogenous DNA encoding a polypeptide. 
   
   
       13 . A method of treating a kidney disease resulting in decreased EPO production in a patient in need thereof, said method comprising:
 providing a composition comprising an isolated population of EPO producing cells in a pharmaceutically acceptable carrier; and   administering said composition to said patient, whereby said EPO producing cells produce EPO in vivo.   
   
   
       14 . The method of  claim 13 , wherein said pharmaceutically acceptable carrier comprises a collagen gel. 
   
   
       15 . The method of  claim 13 , wherein said administering step is carried out by injecting said composition into the kidney or liver of said patient. 
   
   
       16 . The method of  claim 13 , wherein said administering step is carried out by injecting or infusing said composition intravascularly. 
   
   
       17 . The method of  claim 13 , where said administering step is carried out by infusing said composition into a portal vein of said patient. 
   
   
       18 . The method of  claim 13 , wherein said pharmaceutically acceptable carrier comprises a biodegradable scaffold administering step is carried out by implanting said composition into the kidney of said patient. 
   
   
       19 . The method of  claims 13 , wherein said population of EPO producing cells consists essentially of differentiated peritubular interstitial cells. 
   
   
       20 . The method of  claim 13 , subject to the proviso that said EPO producing cells are not transfected with an exogenous DNA encoding a polypeptide. 
   
   
       21 . The method of  claim 13 , wherein said kidney disease is an anemia selected from the group consisting of: an anemia of renal failure, an anemia of end-stage renal disease, an anemia of a chemotherapy, an anemia of a radiation therapy, an anemia of chronic infection, an anemia of an autoimmune disease, an anemia of rheumatoid arthritis, an anemia of AIDS, an anemia of a malignancy, an anemia of prematurity, an anemia of hypothyroidism, an anemia of malnutrition, and an anemia of a blood disorder. 
   
   
       22 . The method of  claim 13 , wherein said administering step is carried out by injecting or implanting said composition. 
   
   
       23 . The method of  claim 13 , wherein said EPO producing cells are human. 
   
   
       24 . An isolated population of cells comprising differentiated human kidney cells harvested from human kidney tissue and passaged in vitro. 
   
   
       25 . The population of cells according to  claim 24 , wherein said differentiated human kidney cells produce erythropoietin (EPO). 
   
   
       26 . The population of cells according to  claim 24 , wherein said population consists essentially of said differentiated human kidney cells. 
   
   
       27 . The population of cells according to  claim 24 , wherein said human kidney cells have been passaged in vitro from 1 to 20 times. 
   
   
       28 . The population of cells according to  claim 24 , wherein said human kidney cells have been passaged in vitro at least 3 times. 
   
   
       29 . The population of cells according to  claim 24 , wherein said population has been selected for EPO production. 
   
   
       30 . The population of cells according to  claim 24 , subject to the proviso that said cells are not transfected with an exogenous DNA encoding a polypeptide. 
   
   
       31 . A composition comprising the population of cells according to  claim 24  and a pharmaceutically acceptable carrier. 
   
   
       32 . The composition of  claim 31 , wherein said carrier comprises collagen. 
   
   
       33 . A method of treating anemia in a patient in need thereof, said method comprising:
 providing a composition comprising the population of cells according to  claim 25 ; and administering said composition to said patient in an amount effective to treat said anemia.   
   
   
       34 . The method of  claim 33 , wherein said administering step is carried out by injecting or implanting said composition into said patient. 
   
   
       35 . The method of  claim 33 , wherein said anemia is selected from the group consisting of: an anemia of renal failure, an anemia of end-stage renal disease, an anemia of a chemotherapy, an anemia of a radiation therapy, an anemia of chronic infection, an anemia of an autoimmune disease, an anemia of rheumatoid arthritis, an anemia of AIDS, an anemia of a malignancy, an anemia of prematurity, an anemia of hypothyroidism, an anemia of malnutrition, and an anemia of a blood disorder.