Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells

Abstract

Cell therapy using human-stem-cell-derived pancreatic beta cells (hSC-bs) is a potential treatment method for type 1 diabetes mellitus (T1D). For therapeutic safety, hSC-bs need encapsulation in grafts that are scalable and retrievable. In this study, we developed a lotus-root-shaped cell-encapsulated construct (LENCON) as a graft that can be retrieved after long-term hSC-b transplantation. This graft had six multicores encapsulating hSC-bs located within 1 mm from the edge. It controlled the recipient blood glucose levels for a long-term, following transplantation in immunodeficient diabetic mice. LENCON xenotransplanted into immunocompetent mice exhibited retrievability and maintained the functionality of hSC-bs for over 1 year after transplantation. We believe that LENCON can contribute to the treatment of T1D through long-term transplantation of hSC-bs and in many other forms of cell therapy.

Advanced strategies to thwart foreign body response to implantable devices

“…The authors suspect this effect can be induced by the higher curvature on the surface of smaller spheres. Analogous observations resulted from the intraperitoneal implantation of cylindrical alginate implants (1 and 6 mm diameters) in mice 147 . The smallest devices had increased cellular deposition that caused a thicker fibrotic layer on their surface.…”

“…Analogous observations resulted from the intraperitoneal implantation of cylindrical alginate implants (1 and 6 mm diameters) in mice. 147 The smallest devices had increased cellular deposition that caused a thicker fibrotic layer on their surface. Similarly, hydrogel fiber diameter appears to have an effect on cellular deposition.…”

Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering

“…In in vivo applications, injectable bead-based scaffolds for wound healing, muscle, or neural regeneration should degrade possibly fast, with the degradation time of the order of weeks. In applications where implanted cells are supposed to act as a cure for prolonged periods of time, such as, e.g., in the case of insulin-producing beta cells , or mesenchymal stem cells, the degradation time should be extended . This is typically achieved by the use of alginate whose mechanical and degradation properties can be additionally tuned, e.g., via adjusting the molecular weight …”

“…Alginate polymers with molecular weight in the range 32–400 kDa find extensive applications in cell encapsulation. In particular, due to the almost immediate cross-linking of alginate upon contact with calcium ions, alginate precursors have been predominantly used as the shell phase in the core–shell capsules ,,,,,,,− and core–shell fibers, ,,,,,,,,− various types of Janus and multicompartment Janus structures, ,, including both capsules ,,,− and fibers ,,,,, as well as all-cross-linked core–shell capsules, ,, microdroplets, and microfibers ,, with complex topology, droplet-loaded fibers, ,, or helical fibers − (see sections and ). 2D structures such as grooved microfibers, , striped segmented hydrogel microsheets are also typically based on alginate (section ).…”

“…Overall, the large-scale production of tailorable “0D” or “1D” microgels opens new perspectives in tissue engineering and regenerative medicine, in particular in restoration of tissues such as muscle, − heart, , bone, or neural tissue or in cell-based therapies for treatment of diseases such as diabetes or infertility …”