Washington University

Genentech, Inc.

Marc R Hammerman

Ross G Clark

Neil Gesundheit

Steven B Miller

Sharon A Rogers

Provided herein is an approach to establish organogenetic tolerance via prior transplantation of pig embryonic pancreas, thereby enabling subsequent implantation of porcine islets in a subject without the need for immune-suppression. In one aspect of the invention, porcine pancreatic primordia are implanted into a mammalian subject, and after a period of time sufficient to induce tolerance, porcine islet cells are implanted in the subject.

Inducement of organogenetic tolerance for pancreatic xenotransplant

Novel methods, tissues and compositions for increasing the pancreatic mass of a mammalian recipient including harvesting immature pancreatic tissue from a mammalian donor and transplanting said tissue into the peritoneal cavity of a mammalian recipient under conditions that allow the pancreatic tissue to become vascularized and mature, thereby developing a functioning chimeric, endocrine pancreas that produces at least insulin in the recipient. The invention also includes mammalian immature pancreatic tissue adapted for transplantation into the peritoneal cavity of a mammalian recipient for increasing the pancreatic mass of the mammalian recipient as well as methods and compositions for treatment of the pancreatic tissue, recipient immunosuppression and recipient co-stimulatory blockade.

Chimeric pancreas

A method and composition for enhancing the development of metanephric tissue upon transplantation into an allogenic or xenogenic host are disclosed. Metanephric tissue is removed from an embryonic donor and is contacted with a composition comprising one or more growth factors for metanephric development. The composition can be administered to the metanephric tissue in vitro prior to implantation of the donor tissue in the transplant recipient, or can be administered in vivo either during or subsequent to the transplantation procedure.

Composition and method for improving function of embryonic kidney transplants

Methods for increasing the nephron mass of a mammalian recipient are disclosed. A metanephros from an allogenic or xenogeneic mammalian donor is implanted next to a recipient's omentum or under the renal capsule of the recipient's kidney. The metanephros becomes vascularized by the recipient's blood vessels, forming a chimeric kidney that produces urine and develops a ureter that facilitates externalization of the urine. A ureter to ureter anastomosis can be subsequently performed to provide fluid communication between the chimeric kidney ureter and a ureter of the recipient.

Chimeric kidney

A method is disclosed that comprises administering insulin-like growth factor-I (IGF-I) to a mammal so as to sustain its biological activity in the mammal comprising administering a therapeutically effective amount of IGF-I to the mammal to provide an exposure to IGF-I for a period of time that stimulates the maximum biological response in the mammal, then discontinuing said administration for a period of time equal to or less than the time period used for administration, and repeating this pattern of administration and discontinuance of administration for a period as long as necessary to achieve or maintain the desired biological response in the mammal.

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St. Louis, MO, United States of America

Marc R Hammerman