Differentiation of human embryonic stem cells
First Claim
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1. A method for lowering blood glucose levels in a mammal, comprising the steps of:
- (a) differentiating a population of definitive endoderm cells into a population of pancreatic endoderm cells,(b) differentiating the pancreatic endoderm cells of step (a) in a DMEM-high glucose medium comprising an exogenous retinoid to obtain a population of pancreatic endocrine precursor cells expressing insulin, NKX6.1 and PDX1, but not expressing CDX2; and
(c) transplanting the population of pancreatic endocrine precursor cells of step (b) into the liver, natural pancreas, renal subcapsular space, omentum, peritoneum, subserosal space, intestine, or a subcutaneous pocket of the mammal, wherein the pancreatic endocrine precursor cells express insulin, lower the blood glucose levels in the mammal and are protected from host immune response when transplanted.
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Abstract
The present invention provides a method for lowering blood glucose levels in an animal by transplanting a population of pancreatic endocrine precursor cells into an animal.
171 Citations
39 Claims
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1. A method for lowering blood glucose levels in a mammal, comprising the steps of:
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(a) differentiating a population of definitive endoderm cells into a population of pancreatic endoderm cells, (b) differentiating the pancreatic endoderm cells of step (a) in a DMEM-high glucose medium comprising an exogenous retinoid to obtain a population of pancreatic endocrine precursor cells expressing insulin, NKX6.1 and PDX1, but not expressing CDX2; and (c) transplanting the population of pancreatic endocrine precursor cells of step (b) into the liver, natural pancreas, renal subcapsular space, omentum, peritoneum, subserosal space, intestine, or a subcutaneous pocket of the mammal, wherein the pancreatic endocrine precursor cells express insulin, lower the blood glucose levels in the mammal and are protected from host immune response when transplanted. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 18, 19, 38)
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11. A method for lowering blood glucose levels in a mammal, comprising the steps of:
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(a) obtaining a population of definitive endoderm cells, (b) differentiating a population of definitive endoderm cells into a population of pancreatic endoderm cells, (c) differentiating the pancreatic endoderm cells of step (b) in a DMEM-high glucose medium comprising an exogenous retinoid to obtain a population of pancreatic endocrine precursor cells expressing NKX6.1 and PDX1, but not expressing CDX2, (d) differentiating the pancreatic endocrine precursor cells of step (c) in a DMEM-high glucose medium to obtain a population of cells expressing insulin; and (e) transplanting the population of insulin expressing cells of step (d) into the liver, natural pancreas, renal subcapsular space, omentum, peritoneum, subserosal space, intestine, or a subcutaneous pocket of the mammal, wherein the pancreatic endocrine precursor cells express insulin, lower the blood glucose levels in the mammal and are protected from host immune response when transplanted. - View Dependent Claims (12, 13, 14, 15, 16, 17)
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20. A method for lowering blood glucose levels in a mammal, comprising the steps of:
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(a) differentiating a population of definitive endoderm cells into a population of pancreatic endoderm cells, (b) differentiating the pancreatic endoderm cells of step (b) in a DMEM-high glucose medium comprising an exogenous retinoid to obtain a population of pancreatic endocrine precursor cells expressing insulin, NKX6.1 and PDX1, but not expressing CDX2, wherein the pancreatic endocrine precursor cells have increased expression of NKX6.1, PFT1a and NGN-3 as compared to pancreatic endocrine cells obtained from pancreatic endoderm cells differentiated in DMEM-low glucose, CMRL and DM-F12, (c) transplanting the population of pancreatic endocrine precursor cells of step (c) into the liver, natural pancreas, renal subcapsular space, omentum, peritoneum, subserosal space, intestine, or a subcutaneous pocket of the mammal, wherein the pancreatic endocrine precursor cells express insulin, lower the blood glucose levels in the mammal and are protected from host immune response when transplanted. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 34, 35, 36, 37, 39)
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31. A method for lowering blood glucose levels in a mammal, comprising the steps of:
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(a) obtaining a population of definitive endoderm cells, (b) differentiating a population of definitive endoderm cells into a population of pancreatic endoderm cells, (c) differentiating the pancreatic endoderm cells of step (b) in a DMEM-high glucose medium comprising an exogenous retinoid to obtain a population of pancreatic endocrine precursor cells expressing insulin, NKX6.1 and PDX1, but not expressing CDX2, wherein the pancreatic endocrine precursor cells have increased expression of NKX6.1, PFT1a and NGN-3 as compared to pancreatic endocrine cells obtained from pancreatic endoderm cells differentiated in DMEM-low glucose, CMRL and DM-F12, (d) differentiating the pancreatic endocrine precursor cells of step (c) in a DMEM-high glucose medium to obtain a population of cells expressing insulin; and (e) transplanting the population of insulin expressing cells of step (d) into the liver, natural pancreas, renal subcapsular space, omentum, peritoneum, subserosal space, intestine, or a subcutaneous pocket of the mammal, wherein the pancreatic endocrine precursor cells express insulin, lower the blood glucose levels in the mammal and are protected from host immune response when transplanted. - View Dependent Claims (32, 33)
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Specification