Collagen encapsulation of insulin-producing cells
Compositions comprising collagen and insulin-producing cells are provided. Processes for making such a collagen and insulin-producing cell compositions are also provided. Methods for controlling, or lowering blood glucose levels and treating metabolic disorders in mammals, including type 1 diabetes, with such compositions are further provided. Methods to prolong insulin-producing cell viability and function in vitro or during transport are also provided.
1 . An immunoprotective collagen construct formed by the steps of:
injecting a polymerizable cell suspension into a mammalian host, said polymerizable cell suspension consisting of collagen and pancreatic islet cells in an aqueous-based suspension, wherein said collagen present in said polymerizable cell suspension comprises soluble oligomeric type I collagen, and said pancreatic islet cells are dispersed throughout said polymerizable cell suspension; and
polymerizing said polymerizable cell suspension in situ to form said immunoprotective collagen construct, wherein said immunoprotective collagen construct has islet-induced collagen-fibril reorganization and alignment.
2 . An injectable immunoprotective polymerizable collagen suspension consisting of Type I oligomeric collagen, allogeneic or xenogeneic insulin-producing cells in an aqueous-based suspension, wherein said allogeneic or xenogeneic insulin-producing cells are dispersed throughout said injectable immunoprotective polymerizable collagen suspension, and the Type I oligomeric collagen in said injectable immunoprotective polymerizable collagen suspension has a concentration between about 1.5 mg/mL and about 5.0 mg/mL, further wherein, upon polymerization of said injectable immunoprotective polymerizable cell suspension, an oligomeric collagen scaffold is formed having a stiffness of 40 Pa to 2 MPa.
3 . The immunoprotective suspension of claim 2 , wherein said injectable immunoprotective polymerizable cell suspension consists of oligomeric type I collagen and allogeneic insulin-producing cells in an aqueous-based suspension.
4 . The immunoprotective suspension of claim 2 , wherein said allogenic insulin-producing cells comprise pancreatic beta cells.
5 . A method of treating a metabolic disorder in a human by:
administering to the human an effective amount of the immunoprotective suspension of claim 2 ; or
implanting into the human a polymerized oligomeric collagen construct consisting of collagen and allogeneic or xenogeneic insulin-producing cells in an aqueous-based suspension wherein said collagen present in said polymerized oligomeric collagen construct comprises oligomeric type I collagen, and said allogeneic or xenogeneic insulin-producing cells are dispersed throughout said polymerized oligomeric collagen construct.
6 . The method of claim 5 , wherein the metabolic disorder is diabetes and an effective amount of the immunoprotective suspension is injected into the human, wherein polymerization of the injected immunoprotective suspension results in the formation of a fibrillar collagen network and encapsulation of the insulin-producing cells in vivo.
7 . The method of claim 6 , wherein the immunoprotective suspension is administered via subcutaneous injection.
8 . The method of claim 5 , which consists of a single step of injecting said immunoprotective suspension into said human.