Lotus-root-shaped cell-encapsulated construct as a retrieval graft for long-term transplantation of human iPSC-derived β-cells
Fumisato Ozawa,
Shogo Nagata,
Haruka Oda,
Shigeharu G. Yabe,
Hitoshi Okochi,
Shoji Takeuchi
Affiliations
Fumisato Ozawa
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Shogo Nagata
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
Haruka Oda
Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Shigeharu G. Yabe
Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Hitoshi Okochi
Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
Shoji Takeuchi
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Corresponding author
Summary: Cell therapy using human-stem-cell-derived pancreatic beta cells (hSC-βs) is a potential treatment method for type 1 diabetes mellitus (T1D). For therapeutic safety, hSC-βs 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-β transplantation. This graft had six multicores encapsulating hSC-βs 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-βs for over 1 year after transplantation. We believe that LENCON can contribute to the treatment of T1D through long-term transplantation of hSC-βs and in many other forms of cell therapy.
