Brown University

Washington University

Other

Mcdonnell Douglas Corporation

Neurotech S.a.

David W Scharp

Paul E Lacy

Keith E Dionne

Paul R Sanberg

Patrick Aebischer

Frank T Gentile

Dwaine F Emerich

Michael J Lysaght

Orion D Hegre

Diane Hoffman

Lisa Christenson

Alfred V Vasconcellos

Thomas J Poteat

Edward H Finke

Alexander Gorkovenko

Alfred V Vasooncellos

Alfred V Vasoohcellos

Camillo Ricordi

The disclosure provides coated mammalian cells, and related reagents, as well as methods for coating mammalian cells, and methods for implanting the coated cells into a human host.

Coating for cells, reagents and methods

An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process. A method for isolating cells within a biocompatible, immunoisolatory implantable vehicle, which protects the isolated cells from attack by the immune system of an individual in whom the vehicle is implanted. A method of providing a needed biological product or metabolic function to an individual, comprising implanting into the individual an immunoisolatory vehicle containing isolated cells which produce the product or provide the metabolic function.

Implantable biocompatible immunoisolatory vehicle for delivery of selected therapeutic products

An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.

Implantable biocompatible immunoisolatory vehicle for the delivery of selected therapeutic products

Implantable biocompatable immunoisolatory vehicle for delivery of

A biocompatable and biostable flexible pouch for use e.g., in implanting cell bodies producing therapeutic agents, featuring, in various aspects, either encapsulated or unencapsulated cell bodies contained within the pouch; and a means for attaching the opening of the pouch to a vascularized tissue pedicle.

Use of pouch for implantation of living cells

A method of forming an implantable and retrievable immunoisolatory vehicles is disclosed, the method comprising the steps of first forming a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of providing a biologically active product or metabolic or immunologic function, said cells being dispersed in a biocompatible hydrogel or extracellular matrix, and then forming around the core a surrounding external biocompatible thermoplastic or hydrogel jacket free of said cells projecting externally thereof, said jacket having molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.

Methods for making immunoisolatary implantable vehicles with a

A method for treatment of a neurodegenerative condition in a patient comprising implanting in the patient at least one immunoisolatory vehicle comprising a corc comprising a volume of at least 1 .mu.l and at least 10.sup.4 living cells which secrete at least one biologically active product, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and an external jacket surrounding the core, the jacket comprising a biocompatible hydrogel or thermoplastic, the jacket being free of cells projecting externally thereof, said jacket having a molecular weight cutoff permitting the passage of the biologically active product from the core through the jacket.

Methods for treatment or prevention of neurodegenerative conditions

A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising a core comprising a volume of at least 1 .mu.l and at least about 10.sup.4 living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient's body to treat diabetes.

Methods for treating diabetes by delivering insulin from biocompatible

Immunoisolatory vehicles having a core and a surrounding jacket are disclosed, the core having a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells capable of secreting a biologically active product or of providing a biological function to a patient, the cells dispersed in a biocompatible matrix formed of a hydrogel or an extracellular matrix component, and the external jacket being permselective, biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biological product or function.

Implantable biocompatible immunoisolatory vehicle for delivery of

A method of making an immunoisolatory vehicle comprised of a core comprising living cells dispersed in a biocompatible matrix is disclosed, the cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to an individual, and an external jacket surrounding said core which is a biocompatible, permselective thermoplastic or hydrogel, said jacket being free of said cells, comprising coextruding a suspension comprising said cells dispersed in a precursor matrix material comprising extracellular matrix components or a biocompatible hydrogel precursor, and a solution of a biocompatible jacket precursor from a nested dual-bore extrusion nozzle, wherein the suspension of (a) is coextruded from the inner bore and the solution of (b) is coextruded from the outer bore of the nozzle, to form said jacket as the solution of (b) and the suspension of (a) arc coextruded; and exposing the vehicle to a treatment that forms a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells and comprising a biocompatible matrix from the precursor matrix of solution (a).

Methods for coextruding immunoisolatory implantable vehicles with a

A method of providing a biologically active molecule or metabolic or immunologic function to a patient, comprising implanting into the body of the patient at least one immunoisolatory vehicle comprising a core comprising a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells dispersed in a biocompatible matrix formed of a hydrogel or extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to the patient; and an external jacket surrounding said core, said jacket being formed from a thermoplastic or hydrogel, said jacket being free of said cells projecting externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biologically active product of function.

A method of producing intact islets of Langerhans in an insulin producing condition uses a mixture of Hank's solution and 10% by volume fetal calf serum to ductally distend the human pancreas. The exocrine tissue of the pancreas is digested at about 37.degree. C. by an enzyme preparation of collagenase, trypsin and proteolytic enzyme present in the mixture at a level of about 0.2% by weight. The digestion is monitored at regular intervals during the process. The digested pancreas is comminuted, filtered and intact islets of Langerhans are recovered. The recovered islets retain their insulin producing properties.

Islet isolation process

A method to obtain purified, well-defined cell populations from intact organs uses digestion of the distended organ with suitable proteolytic enzymes and harvest of the cell subpopulation by screening the effluent from treatment of the organ with physiologically compatible medium by a filtration screen permitting the passage of the desired cells or clusters of cells, but preventing the passage of larger particles. In this manner, physical/mechanical disruption of the cell population is unnecessary, and the cells or clusters are eased out of their structural matrix and harvested directly. Application of this method to the preparation of purified Islets of Langerhans from intact pancreas is described.

Growing community of inventors

St. Louis, MO, United States of America

David W Scharp