Stem cells and their use in transplantation
First Claim
1. A method of treating a patient with diabetes mellitus, comprising the steps of:
- (a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor; and
(b) transferring the stem cell into the patient, wherein the stem cell differentiates into an insulin-producing cell, wherein the patient does not serve as the donor for said stem cells of step a.
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Accused Products
Abstract
Methods and compositions are described for the treatment of type I insulin-dependent diabetes mellitus and other conditions using newly identified stem cells that are capable of differentiation into a variety of pancreatic islet cells, including insulin-producing beta cells, as well as hepatocytes. Nestin has been identified as a molecular marker for pancreatic stem cells, while cytokeratin-19 serves as a marker for a distinct class of islet ductal cells. Methods are described whereby nestin-positive stem cells can be isolated from pancreatic islets and cultured to obtain further stem cells or pseudo-islet like structures. Methods for ex vivo differentiation of the pancreatic stem cells are disclosed. Methods are described whereby pancreatic stem cells can be isolated, expanded, and transplanted into a patient in need thereof, either allogeneically, isogeneically or xenogenically, to provide replacement for lost or damaged insulin-secreting cells or other cells.
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Citations
127 Claims
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1. A method of treating a patient with diabetes mellitus, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor; and
(b) transferring the stem cell into the patient, wherein the stem cell differentiates into an insulin-producing cell, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A method of treating a patient with diabetes mellitus, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) culturing the stem cell ex vivo; and
(c) transferring the progenitor cell into the patient, wherein the progenitor cell differentiates into an insulin-producing beta cell, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (14, 15, 17, 18, 20, 21, 22, 23, 24)
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13. A method of treating a patient with diabetes mellitus, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell ex vivo to produce a progenitor cell; and
(c) transferring the progenitor cell into the patient, wherein the progenitor cell differentiates into an insulin-producing beta cell, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (16, 19)
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25. A method of treating a patient with diabetes mellitus, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell to produce a progenitor cell;
(c) differentiating the progenitor cell in culture to form pseudo-islet like aggregates; and
(d) transferring the pseudo-islet like aggregates into the patient, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
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36. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor; and
(b) transferring the stem cell into the mammal, wherein the stem cell differentiates into an insulin-producing cell. - View Dependent Claims (37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48)
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49. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) culturing the stem cell ex vivo; and
(c) transferring the progenitor cell into the mammal, wherein the progenitor cell differentiates into an insulin-producing beta cell. - View Dependent Claims (51, 52, 53, 54, 56, 57, 59, 60, 61, 65, 66)
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50. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell ex vivo to produce a progenitor cell; and
(c) transferring the progenitor cell into the mammal, wherein the progenitor cell differentiates into an insulin-producing beta cell. - View Dependent Claims (55, 58, 62, 63, 64)
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67. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell to produce a progenitor cell;
(c) differentiating the progenitor cell in culture to form pseudo-islet like aggregates; and
(d) transferring the pseudo-islet like aggregates into the mammal. - View Dependent Claims (68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79)
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- 80. A transplant graft comprising an isolated, nestin-positive human pancreatic stem cell that is not a neural stem cell.
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85. A method of treating a patient with liver disease, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor; and
(b) transferring the stem cell into the patient, wherein the stem cell differentiates into a hepatocyte, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (88, 89, 90, 91, 93, 94, 95, 96, 97, 98, 99)
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86. A method of treating a patient with liver disease, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell ex vivo to produce a progenitor cell; and
(c) transferring the progenitor cell into the patient, wherein the progenitor cell differentiates into a hepatocyte, wherein the patient does not serve as the donor for said stem cells of step a.
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87. A method of treating a patient with liver disease, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) differentiating the stem cell ex vivo to produce a hepatocyte; and
(c) transferring the hepatocyte into the patient, wherein the patient does not serve as the donor for said stem cells of step a. - View Dependent Claims (92)
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100. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor; and
(b) transferring the stem cell into said mammal, wherein the stem cell differentiates into a hepatocyte. - View Dependent Claims (101, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117)
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102. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) expanding the stem cell ex vivo to produce a progenitor cell; and
(c) transferring the progenitor cell into said mammal, wherein the progenitor cell differentiates into a hepatocyte. - View Dependent Claims (103)
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104. A method of transplanting into a mammal, comprising the steps of:
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(a) isolating a nestin-positive pancreatic stem cell from a pancreatic islet of a donor;
(b) differentiating the stem cell ex vivo to produce a hepatocyte; and
(c) transferring the hepatocyte into said mammal. - View Dependent Claims (105)
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- 118. A transplant graft comprising an isolated, nestin-positive human liver stem cell that is not a neural stem cell.
- 123. A transplant graft comprising an isolated, nestin-positive human stem cell that is not a neural stem cell, that is capable of transplant into an animal without causing graft versus host rejection.
Specification