Formulations for pancreatic islet encapsulation
Provided herein according to embodiments of the present invention is a microcapsule comprising: (a) one or more live mammalian pancreatic islet cells; and (b) an alginate composition encapsulating said islet cells, wherein said alginate composition comprises extracellular matrix proteins solubilized or suspended therein. Compositions comprising a plurality of the microcapsules and the use thereof in treating type I diabetes are also provided.
1 . A microcapsule comprising:
(a) one or more live mammalian pancreatic islet cells; and
(b) an alginate composition encapsulating said islet cells,
wherein said alginate composition comprises extracellular matrix proteins solubilized therein,
wherein said extracellular matrix proteins are pancreatic extracellular matrix proteins obtained from a decellularized extracellular pancreatic matrix,
wherein said extracellular matrix proteins are present in an amount of from 0.5 mg per mL to 10 mg per mL of the alginate composition,
wherein said alginate composition is a high-mannuronic acid (high-M) alginate composition,
wherein said alginate composition is crosslinked with Sr ++ , and
wherein said alginate composition has a storage modulus of from about 0.1 to about 6 kiloPascals.
2 . The microcapsule of claim 1 , wherein said extracellular matrix proteins are human extracellular matrix proteins.
3 . The microcapsule of claim 1 , wherein said alginate composition is coated with poly-L-lysine and/or poly-L-ornithine.
4 . The microcapsule of claim 1 , wherein said cells are human cells.
5 . A composition comprising a plurality of microcapsules of claim 1 .
6 . The composition of claim 5 , wherein the live mammalian pancreatic islet cells are present at a concentration of about 10 3 to about 10 4 islet cells per milliliter of the alginate composition.
7 . The composition of claim 5 , further comprising a pharmaceutically acceptable carrier.
8 . A method of treating diabetes in a subject in need thereof, comprising administering the composition of claim 5 to said subject in a treatment-effective amount.
9 . The method of claim 8 , wherein said administering comprises transplanting the composition into the peritoneal cavity and/or the omentum of the subject.
10 . The method of claim 8 , wherein the cells and/or extracellular matrix proteins are autologous with respect to the subject.
11 . The microcapsule of claim 1 , wherein said Sr ++ is provided in the form of about 12.5, 25, or 50 mM SrCl 2 .
12 . The composition of claim 7 , wherein the pharmaceutically acceptable carrier is endotoxin-free and/or pyrogen-free saline.
13 . The microcapsule of claim 1 , wherein said alginate composition has a storage modulus of from about 1 to about 4 kiloPascals.
14 . The microcapsule of claim 1 , wherein said Sr ++ is provided in the form of about 25 mM SrCl 2 .
15 . The microcapsule of claim 1 , wherein said cells are pig cells.