REVERSAL OF INSULIN-DEPENDENT DIABETES BY ISLET-PRODUCING STEM CELLS, ISLET PROGENITOR CELLS AND ISLET-LIKE STRUCTURES
First Claim
1. A method for growing islet producing stem cells (IPSCs), islet progenitor cells (IPCs) and IPC-derived islets (IdIs) comprising the steps ofa) culturing pancreatic cells from a mammalian species in vitro in a basal medium comprising serum less than about 0.5%, and glucose less than about 1 mM, undisturbed for at least 3 weeks, whereby an epithelial monolayer containing IPSCs is produced, andb) initiating cellular differentiation, whereby IPCs and IdIs are produced.
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Abstract
The subject invention concerns new methods which make it possible, for the first time, to grow functional islet-producing stem cells (IPSCs), islet progenitor cells (IPCs) and IPC-derived islets (IdIs) in in vitro cultures. The subject invention also concerns the use of the in vitro grown IPSCs, IPCs and/or IdIs for implantation into a mammal for in vivo therapy of diabetes. The subject invention further concerns a process of using the implanted cells for growing a pancreas-like structure in vivo that has the same functional, morphological and histological characteristics as those observed in normal pancreatic endocrine tissue. The ability to grow these cells in vitro and pancreas-like structures in vivo opens up important new avenues for research and therapy relating to diabetes.
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Citations
24 Claims
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1. A method for growing islet producing stem cells (IPSCs), islet progenitor cells (IPCs) and IPC-derived islets (IdIs) comprising the steps of
a) culturing pancreatic cells from a mammalian species in vitro in a basal medium comprising serum less than about 0.5%, and glucose less than about 1 mM, undisturbed for at least 3 weeks, whereby an epithelial monolayer containing IPSCs is produced, and b) initiating cellular differentiation, whereby IPCs and IdIs are produced.
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2. An in vitro produced IPC-derived islet (IdI) comprising β
- cells and either α
or PP cells, wherein said β
cells are located in the center of the IdI, said α
or PP cells are located in an outer cortex of the IdI, and proliferating and undifferentiated cells are located in an inner cortex of the IdI, wherein about 20 to 25% of the total cells of said IdI are β
cells. - View Dependent Claims (5, 6, 7, 8, 9)
- cells and either α
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3. An IdI comprising β
- cells located in the center of the IdI, α
or PP cells located in an outer cortex of the IdI, and proliferating and undifferentiated cells located in an inner cortex of the IdI, wherein about 20 to 25% of the total cells of said IdI are β
cells, produced according to a method comprising the steps of;a) culturing pancreatic cells from a mammalian species in vitro in a basal medium comprising serum less than about 0.5%, and glucose less than about 1 mM, undisturbed for at least 3 weeks, whereby an epithelial monolayer containing IPSCs is produced, and b) initiating cellular differentiation, whereby IPCs and IdIs are produced. - View Dependent Claims (4)
- cells located in the center of the IdI, α
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10. A method of treating pancreatic disease or producing a pancreas-like structure in a mammal which comprises the steps of
a) culturing pancreatic cells from a mammalian species in vitro under conditions that are favorable to the survival of IPSCs and ductal epithelial cells, and substantially lethal to differentiated cells, whereby a ductal epithelial monolayer containing IPSCs is produced, b) initiating cellular differentiation, whereby IPCs and IdIs are produced, c) implanting in a mammal a composition comprising said IdIs and optionally cells or tissue selected from the group consisting of said ductal epithelium, IPSCs, and IPCs and any combination thereof, whereby a pancreas-like structure and islet hormones are produced, providing for the treatment of the pancreatic disease.
- 19. A method for long-term propagation of IPSCs which comprises serially transferring a cellular composition comprising IdIs and optionally material selected from the group consisting of ductal epithelium, IPSCs, IPCs and any combination thereof.
- 21. A method for inducing neovascularization in a pancreatic implant in a mammal comprising transplanting into said mammal the pancreatic implant comprising IdIs and optionally cells or tissue selected from the group consisting of IPSCs and IPCs, whereby vascularization is induced or enhanced.
- 23. A structure consisting essentially of a pancreas-like structure produced by implantation of IdIs and optionally cells or tissues selected from the group consisting of IPSCs and IPCs, and comprising at least 50% by weight of endocrine tissue.
Specification