Selective cell therapy for the treatment of renal failure
First Claim
1. A composition suitable for administration to the kidney of a subject comprising a population of differentiated mammalian renal cells harvested from the subject'"'"'s kidney and passaged in vitro from 2 to 9 times to expand their number, wherein the population comprises renal cells that produce erythropoietin (EPO) in co-culture with other cortical renal cell types, and a pharmaceutically acceptable carrier,wherein:
- (i) the renal cells produce EPO under normoxic conditions, and(ii) the cells that produce EPO and the other cortical renal cell types have not been manipulated by the introduction of an exogenous gene that stimulates the production of EPO or by an exogenous chemical that stimulates the production of EPO,subject to the proviso that said cells that produce EPO and other cortical renal cell types are not transfected with an exogenous DNA encoding a polypeptide,wherein said population has oxygen tension-dependent EPO expression such that the cells that produce EPO have a 2- to 20-fold increase in EPO expression as measured by an increase in EPO mRNA when under hypoxic conditions as compared to normoxic conditions, and have a 2- to 20-fold decrease in EPO expression as measured by a decrease in EPO mRNA expression when cells return to normoxic conditions from hypoxic conditions,wherein said pharmaceutically acceptable carrier comprises a hydrogel,wherein said composition comprises from 1×
105 to 1×
109 total renal cells, andwherein said population expresses EPO in vivo upon administration to the subject.
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Abstract
Provided herein are isolated populations of kidney cells harvested from differentiated cells of the kidney, wherein the cells have been expanded in vitro. The kidney cells 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 express EPO in vivo in an oxygen tension-dependent manner.
77 Citations
10 Claims
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1. A composition suitable for administration to the kidney of a subject comprising a population of differentiated mammalian renal cells harvested from the subject'"'"'s kidney and passaged in vitro from 2 to 9 times to expand their number, wherein the population comprises renal cells that produce erythropoietin (EPO) in co-culture with other cortical renal cell types, and a pharmaceutically acceptable carrier,
wherein: -
(i) the renal cells produce EPO under normoxic conditions, and (ii) the cells that produce EPO and the other cortical renal cell types have not been manipulated by the introduction of an exogenous gene that stimulates the production of EPO or by an exogenous chemical that stimulates the production of EPO, subject to the proviso that said cells that produce EPO and other cortical renal cell types are not transfected with an exogenous DNA encoding a polypeptide, wherein said population has oxygen tension-dependent EPO expression such that the cells that produce EPO have a 2- to 20-fold increase in EPO expression as measured by an increase in EPO mRNA when under hypoxic conditions as compared to normoxic conditions, and have a 2- to 20-fold decrease in EPO expression as measured by a decrease in EPO mRNA expression when cells return to normoxic conditions from hypoxic conditions, wherein said pharmaceutically acceptable carrier comprises a hydrogel, wherein said composition comprises from 1×
105 to 1×
109 total renal cells, andwherein said population expresses EPO in vivo upon administration to the subject. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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Specification