Artificial pancreatic perfusion device with temperature sensitive matrix

Claim 1

An artificial pancreatic perfusion device for providing insulin to an individual, the device comprising: a) a hollow fiber having one end connected to a blood vessel through a connecting means to receive blood from the individual and an opposite end connected to a blood vessel through a second connecting means to return blood to the individual, the hollow fiber having a porosity which selectively allows substances to pass transversely therethrough, such that blood flows within the hollow fiber, along the length of the fiber; and b) a housing containing a suspension of pancreatic islets of Langerhans, the suspension including pancreatic islets distributed in a temperature sensitive supporting material about the hollow fiber such that the hollow fiber is surrounded by pancreatic islets along its length, the supporting material characterized by (i) being sufficiently viscous at temperatures below about 45° C. to maintain distribution of the islets with respect to the hollow fiber, and (ii) being sufficiently fluid at temperatures above about 45° C. to enable removal of the islet suspension for subsequent replacement thereof.

Claim 10

A method for seeding a device with islets of Langerhans on multiple occasions before and after use of the device for the production of insulin, comprising the steps of: (a) forming an islet suspension by distributing the islets in a temperature sensitive supporting material sufficiently viscous at temperatures below about 45° C. to physically suspend the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the islet suspension from the device as desired; (b) introducing a first portion of islet suspension into the device, such first portion sufficient for the production of a desired amount of insulin by the device, wherein such first portion is in a semi-gel state; (c) cooling to form a semi-solid matrix; (d) subsequently warming to convert the semi-solid matrix to a semi-gel; (e) withdrawing some or all of said first portion of islet suspension from the device; and (f) introducing a second portion of islet suspension into the device, such second portion sufficient for the production of a desired amount of insulin by the device, wherein such second portion is in a semi-gel state.

Claim 11

A method for seeding a device with islets of Langerhans on multiple occasions before and after use of the device for the production of insulin, comprising the steps of: (a) forming an islet suspension by distributing the islets in a temperature sensitive supporting material sufficiently viscous at temperatures below about 45° C. to physically suspend the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the islet suspension from the device as desired; (b) introducing a first portion of islet suspension into the device, such first portion sufficient for the production of a desired amount of insulin by the device, wherein such first portion is in a semi-gel state; (c) cooling to form a semi-solid matrix; (d) subsequently warming to convert the semi-solid matrix to a semi-gel; (e) withdrawing some or all of said first portion of islet suspension from the device; and (f) introducing a second portion of islet suspension into the device, such second portion sufficient for the production of a desired amount of insulin by the device, wherein such second portion is in a semi-gel state.

Claim 16

A method of preparing islets of Langerhans for use in a device, comprising the steps of: (a) providing islets; (b) combining the islets with cell culture medium and a sufficient amount of a supporting material to form an islet mixture, the supporting material being sufficiently viscous at temperatures below about 45° C. to maintain suspension of the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the inlet suspension from the device; and (c) storing the islet mixture under in vitro culture conditions suitable for maintaining islets; and (d) forming a pipettable islet suspension phase from an amount of the islet mixture, by removing the cell culture medium from the islet mixture.

Claim 17

A method of preparing islets of Langerhans for use in a device, comprising the steps of: (a) providing islets; (b) combining the islets with cell culture medium and a sufficient amount of a supporting material to form an islet mixture, the supporting material being sufficiently viscous at temperatures below about 45° C. to maintain suspension of the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the inlet suspension from the device; and (c) storing the islet mixture under in vitro culture conditions suitable for maintaining islets; and (d) forming a pipettable islet suspension phase from an amount of the islet mixture, by removing the cell culture medium from the islet mixture.

Claim 20

A method of preparing islets of Langerhans for use in a device, comprising the steps of: (a) providing islets; (b) combining the islets with cell culture medium and a sufficient amount of a supporting material to form an islet mixture, the supporting material being sufficiently viscous at temperatures below about 45° C. to maintain suspension of the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the islet suspension from the device; (c) storing the islet mixture under in vitro culture conditions suitable for maintaining islets; (d) warming the islet mixture to at least about 45° C.; (e) removing the islet mixture from in vitro culture; (f) centrifuging the islet mixture to form a culture medium phase and an islet suspension phase; and (g) isolating the islet suspension phase for use in the device.

Claim 21

A method of preparing islets of Langerhans for use in a device, comprising the steps of: (a) providing islets; (b) combining the islets with cell culture medium and a sufficient amount of a supporting material to form an islet mixture, the supporting material being sufficiently viscous at temperatures below about 45° C. to maintain suspension of the islets and sufficiently fluid at temperatures above about 45° C. to enable removal of the islet suspension from the device; (c) storing the islet mixture under in vitro culture conditions suitable for maintaining islets; (d) warming the islet mixture to at least about 45° C.; (e) removing the islet mixture from in vitro culture; (f) centrifuging the islet mixture to form a culture medium phase and an islet suspension phase; and (g) isolating the islet suspension phase for use in the device.