The present disclosure provides cell-based compositions for treating diabetes, methods for identifying cells that preferentially differentiate into endoderm cells, and methods for preparing insulin-producing pancreatic cells, as well as related methods of use for treating diseases related to insulin deficiency.

Described are Neo-Islets comprising: a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells where the cells have been treated so as to facilitate redifferentiation. Further described herein are methods of generating Neo-Islets, the methods comprising: culturing a) dedifferentiated islet cells and mesenchymal and/or adipose stem cells; or b) redifferentiated islet cells and mesenchymal and/or adipose stem cells; on a surface that promotes the formation of cell clusters. Also described are methods of treating a subject, the methods comprising: providing to the subject Neo-Islets described herein. Additionally described are methods of treating a subject suffering from Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and other types of insulin-dependent diabetes mellitus, or impaired glucose tolerance by providing to the subject Neo-Islet as described herein. Additionally described are methods of treatment in which intraperitoneal administration of islet-sized Neo-Islets composed of high numbers of mesenchymal stem cells and cultured islet cells, durably and reversibly treats, without hypoglycemia, both streptozotocin-induced and spontaneous Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and other types of insulin-dependent diabetes mellitus, or impaired glucose tolerance.

The present disclosure provides cell-based compositions for treating diabetes, methods for identifying cells that preferentially differentiate into endoderm cells, and methods for preparing insulin-producing pancreatic cells, as well as related methods of use for treating diseases related to insulin deficiency.

Provided herein are endocrine progenitor cells and organoids derived from adult islets in vitro, as well as methods for making and using the same. The compositions are useful for treating or preventing diabetes, other diseases or disorders characterized by impaired islet function, and symptoms thereof.

As an approach of efficiently inducing differentiation from pluripotent stem cells into insulin-producing cells, provided is a method comprising the step of three-dimensionally culturing cells in a medium containing a dihydroindolizinone derivative.

The present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials. A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

A method for producing at least one microneedle containing a vaccine for transdermal delivery of the vaccine to a patient includes preparing microparticles or nanoparticles of encapsulated vaccine by preparing a solution comprising a vaccine antigen and a biocompatible polymer matrix; and spray drying the solution to form the microparticles or nanoparticles. The method includes the further steps of preparing a film composition including at least one pre-polymer solution; preparing a suspension comprising the microparticles or nanoparticles and the film composition; loading the suspension into a 3D printer; printing, via the 3D printer, at least one microneedle made from the suspension; and, converting the pre-polymer solution into a cross-linked biopolymer by exposing the at least one microneedle to UV light. Also disclosed are microneedles containing a vaccine for transdermal delivery.

A tissue construct is provided that comprises a pancreas derived microvessel fragment and a pancreatic islet cell. The pancreas derived microvessel fragment and the pancreatic islet cell can be incorporated into a biocompatible medium. Tissue constructs can be comprised of other cells, such as stem cells, combined with the pancreas derived microvascular fragment. Methods for isolating microvessel fragments from a pancreas are also provided and include enzymatic digestion of pancreatic tissue and separation of microvessel fragments from endocrine and exocrine tissue. Methods for treating diabetes are further provided and include administration of the tissue constructs.

Disclosed are devices and methods for transplanting cells, such as pancreatic endoderm cells, into a host. The devices include a non-woven fabric external to a cell-excluding membrane, and the non-woven fabric and/or cell-excluding membrane can be perforated. Treatment of the host with immunosuppressive reagents, required to inhibit allograft rejection due to perforations in the cell delivery device, does not compromise maturation or function of transplanted pancreatic endoderm cells.

According to the present invention, there are provided a chamber for transplantation, as a planar chamber for transplantation which has a structure in which membranes for immunoisolation face each other, and which is capable of stably enclosing a biological constituent, including a membrane for immunoisolation at a boundary between an inside and an outside of the chamber for transplantation, in which the membranes for immunoisolation which face each other have joint portions that are joined to each other, an interior space includes a point at a distance of 10 mm or longer from any position of the joint portion, and the membrane for immunoisolation has flexibility that allows a distance of 1 mm to 13 mm as the following distance: in a case where a portion of 10 mm from a side surface of one short side of a 10 mm×30 mm rectangular test piece of the membrane for immunoisolation is vertically sandwiched between flat plates, and the flat plates are placed horizontally, a distance between a horizontal plane including a center plane in a thickness direction of the sandwiched portion of the membrane for immunoisolation, and a part, which is farthest from the horizontal plane, of a residual 20 mm-portion projecting from the flat plate; and a device for transplantation including the chamber for transplantation enclosing a biological constituent therein.