Macro-encapsulated therapeutic cells, devices, and methods of using the same
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Publication Number
US-11141508-B2
Publication Date
2021-10-12
Expiration Date
Abstract
Described are macro-capsules, barriers, and devices that can be used to prepare therapeutic cell implants, methods of encapsulating therapeutic cells, and methods of using the encapsulated cells in the treatment of disease.
Core Innovation
The disclosure provides macro-encapsulated therapeutic cells for diabetes, including insulin-producing therapeutic cells. A device and compositions are described in which therapeutic cells are encompassed by a macro-capsule that includes a first barrier and a second barrier, where the first barrier is encompassed within the second barrier. The barrier chemistry of the first barrier includes cellulose sulfate with glucomannan or glucomannan sulfate, or alternatively sodium alginate.
In the described embodiments, the macro-capsule has a cylindrical shape with a diameter of at least 1.5 mm. The macro-capsules encompass a plurality of insulin-producing therapeutic cells, and the macro-capsules are attached to a piece of surgical mesh. Multiple macro-capsules are included in a plurality, with each macro-capsule comprising at least a first barrier and a second barrier and having the specified minimum diameter.
The document further emphasizes scaling and implantation architecture by attaching the macro-capsules to surgical mesh using retrievable implantation locations. Example implantation locations described include the greater omentum, an omentum pouch, and the peritoneal cavity, with the device being retrievable at implantation sites.
The disclosed barrier designs and macro-capsule dimensions are presented as enabling high cell loading and improved host response. The document reports permeability of the macro-capsules, including passage of molecules such as 20 kDa dextran, and describes engraftment in a diabetic rat model with blood glucose regulation, vascularization, insulin expression, and minimal inflammation and fibrosis.
Claims Coverage
The independent claims are 1, 10, 19, and 33. Across these claims, there are inventive features covering barrier chemistry, a first barrier encompassed within a second barrier, cylindrical macro-capsules with specified minimum diameters and in some claims additional size constraints, attachment of macro-capsules to surgical mesh for device and composition architectures, and one claim family also includes quantitative cell-loading thresholds and a two-stage macro-capsule-to-mesh arrangement.
Two-barrier macro-capsule with specific first barrier chemistry
A macro-capsule encompassing therapeutic cells wherein the macro-capsule comprises a first barrier and a second barrier encompassing the first barrier, wherein the first barrier comprises cellulose sulfate and glucomannan or glucomannan sulfate, or sodium alginate.
Cylindrical macro-capsule diameter and mesh attachment
The macro-capsule has a cylindrical shape and a diameter of at least 1.5 mm, wherein the macro-capsules are attached to a piece of surgical mesh.
Cylindrical insulin-producing macro-capsule composition attached to mesh
A composition comprising a cylindrical macro-capsule encompassing a plurality of insulin-producing therapeutic cells, the macro-capsule comprising a first barrier and a second barrier, wherein the macro-capsule is attached to a piece of surgical mesh to which at least one other macro-capsule is also attached, and wherein the diameter of the macro-capsule is at least 1.5 mm.
First barrier encompassed within second barrier across multiple macro-capsules attached to mesh
A composition comprising a plurality of macro-capsules encompassing a plurality of insulin-producing therapeutic cells, each macro-capsule comprising at least a first barrier and a second barrier, wherein the first barrier is encompassed within the second barrier, wherein each macro-capsule has a diameter of at least 1.5 mm, and wherein each macro-capsule in the plurality of macro-capsules is attached to a piece of surgical mesh.
Macro-capsule with quantitative cell loading and defined cylinder dimensions attached to mesh
A composition comprising a macro-capsule encompassing at least 50,000 insulin-producing therapeutic cells per cm, the macro-capsule comprising a cylindrical shape and a diameter of at least 1.5 mm, wherein the macro-capsule is attached to a piece of surgical mesh to which at least one other macro-capsule is also attached, wherein the macro-capsule comprises at least a first barrier and a second barrier, wherein the first barrier is encompassed within the second barrier, and wherein the first barrier comprises cellulose sulfate and glucomannan or glucomannan sulfate, or sodium alginate.
Overall, the claim coverage centers on macro-capsules with a first barrier inside a second barrier using specified barrier chemistries, cylindrical macro-capsule dimensions, macro-capsule attachment to surgical mesh in single or multiple macro-capsule arrangements, and in one independent claim a quantitative cell loading requirement.
Stated Advantages
Improved permeability, including passage of ~20 kDa dextran.
Reduced fibrosis and minimal inflammation/host immune adhesion.
Vascularization and maintenance of viability and insulin expression after implantation.
Blood glucose regulation in a diabetic rat model.
Documented Applications
Treatment of diabetes by implanting a device comprising a surgical mesh with macro-capsules encompassing insulin-producing therapeutic cells into a subject’s greater omentum or peritoneal cavity.
Use of the macro-encapsulated insulin-producing therapeutic cells for engraftment and blood glucose regulation in a diabetic rat model.
Example implantation and explant evaluation including assessment of vascularization, insulin expression, and inflammation/fibrosis.
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