Preparation and xenotransplantation or porcine islets
First Claim
1. A method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising:
- (i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, the culture of the harvested pancreas being—
(a) of mechanically reduced harvested pancreas, and (b) a supportive mammalian albumin substantially free of non-human microbiological agents, wherein (at least some stage in the method) the islets are associated with Sertoli cells.
3 Assignments
0 Petitions
Accused Products
Abstract
The invention relates to a method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising: (i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, (iii) the culture of the harvested pancreas being a) of mechanically reduced harvested pancreas, and b) a supportive mammalian albumin substantially free of non-human microbiological agents,wherein (at least some stage in the method) the islets are associated with Sertoli cells. The preparations is preferably used in one of two implantation devices, the method of preparation of which are disclosed: a vascularised subcutaneous collagen tube, a capsule formed from a biocompatible xenotransplantable material Further disclosed are methods of treating a mammalian patient predisposed to or suffering from diabetes which involves the xenotransplantation into such patient an implantation device of the invention.
-
Citations
66 Claims
-
1. A method of preparing a xenotransplantable porcine islet preparation capable upon xenotransplantation of producing porcine insulin in an appropriate recipient mammal, the method including or comprising:
-
(i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, the culture of the harvested pancreas being— (a) of mechanically reduced harvested pancreas, and (b) a supportive mammalian albumin substantially free of non-human microbiological agents, wherein (at least some stage in the method) the islets are associated with Sertoli cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
-
-
17. A method of preparing an implantable device which Includes at least one xenotransplantable porcine islet capable upon xenotransplantation of producing porcine Insulin in an appropriate recipient mammal, said method including all comprising:
-
(i) harvesting the pancreas of a piglet or piglets at −
20-+20 days of full term gestation(ii) mechanically reducing the harvested pancreas in the presence of an islet trauma protecting agent and producing a culture of the mechanically reduced harvested pancreas supported by human serum albumin (HSA), (iii) isolating the islet cells from the culture of mechanically reduced harvested pancreas using a collagenase selected from human Liberase® and
porcine Liberase®
, and(iv) incorporation of the islets cells in a device suitable for implantation into a recipient mammal, wherein nicotinamide is introduced to the islets or islet cells prior to incorporationat any one or more stages of the procedure, and wherein, at least to the extent required to convert porcine non insulin producing islet cells to porcine insulin producing islet cells, at some stage in the procedure presenting the islets and/or islet cells to IgF-1 or the N-terminal tripeptide of IgF-1 (GPE), and wherein (at least at some stage in the method) the islet cells are associated with Sertoli cells. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 43)
-
-
31. A vascularised subcutaneous tube containing viable islet cells from a −
- 20 to +20 full term gestation piglet capable of producing porcine insulin in response to glucose within a recipient mammal,
the tube in vivo limiting the egress of the islet cells and allowing an abundant access to blood vessels, the tube also employing or containing Sertoli cells to substantially reduce or prevent tissue immune rejection within the recipient mammal. - View Dependent Claims (32, 33, 34, 35)
- 20 to +20 full term gestation piglet capable of producing porcine insulin in response to glucose within a recipient mammal,
-
36. A xenotransplantable capsule having viable islet cells from a −
- 20 to +20 full term gestation piglet capable of producing porcine insulin in response to glucose within a recipient mammal within its biocompatible encapsulating material or materials, the capsule being such that the encapsulation is such as to prevent tissue contact with said islet cell(s) by tissue of a recipient mammal yet in vivo will allow glucose entry to the islet cells and the egress of porcine insulin from such islet cells, wherein the islet cells are associated with Sertoli cells.
- View Dependent Claims (37, 38, 39, 40, 41, 42)
-
44. A method for the treatment of a mammalian patient suffering from or predisposed to diabetes, said method including or comprising the steps of:
-
(A) (i) harvesting the pancreas of piglets at or near full term gestation, (ii) culturing the harvested pancreas in mammalian albumin substantially free of non-human microbiological agents, (iii) simultaneously with step (ii) and/or after step (ii), extracting the islets from the harvested pancreas using a suitable Liberase®
,wherein the islets (at least at some stage in the performance of (A)) are exposed to nicotinamide;
(B) (i) incorporation of the islets cells, together with Sertoli cells in a device or vehicle suitable for delivery or implantation or xenotransplantation into the recipient mammal, (ii) implanting the islets so incorporated into the recipient mammal. - View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52)
-
-
53. A method of preparing an implant which includes at least one xenotransplantable porcine islet capable upon xenotransplantation of producing porcine Insulin in an appropriate recipient mammal including the steps of:
-
preparation of porcine pancreatic islets, preparation of Sertoli cells, preparation of the implant incorporating the Sertoli cells and porcine islets. - View Dependent Claims (54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)
-
Specification