Yusuke Katsuki1, Hiroshi Yagi2, Teru Okitsu3, Minoru Kitago4, Kazuki Tajima5, Yoshie Kadota6, Taizo Hibi7, Yuta Abe8, Masahiro Shinoda9, Osamu Itano10, Shoji Takeuchi11, Yuko Kitagawa12. 1. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: yours1008@gmail.com. 2. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: h_yagi@a3.keio.jp. 3. Center for International Research on Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Meguro, Tokyo 153-8505, Japan. Electronic address: okitsu@iis.u-tokyo.ac.jp. 4. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: dragonpegasus427@gmail.com. 5. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: tajima-k@hotmail.co.jp. 6. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: yoshiekadota@gmail.com. 7. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: taizohibi@z3.keio.jp. 8. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: abey3666@gmail.com. 9. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: masa02114@yahoo.co.jp. 10. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: itano@z8.keio.jp. 11. Center for International Research on Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Meguro, Tokyo 153-8505, Japan. Electronic address: takeuchi@iis.u-tokyo.ac.jp. 12. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Electronic address: kitagawa@a3.keio.jp.
Abstract
OBJECTIVES: Because therapeutic options for severe diabetes are currently limited, there is a continuing need for new therapeutic strategies, especially in the field of regenerative medicine. Collaborative efforts across the fields of tissue engineering technology and islet biology may be able to create functionally engineered islets capable of restoring endocrine function in patients with insulin-dependent diabetes. METHODS: This engineered scaffold was seeded with isolated primary porcine islets via the pancreatic duct using a multi-step infusion technique. Endocrine function of perfusion-cultured islets in the native scaffold was analyzed by immunohistochemical staining of insulin and glucagon as well as by the insulin stimulation test. RESULTS: The pancreas in this large animal could be uniformly decellularized by perfusion with trypsin and TritonX-100 via the pancreatic duct, as shown by positive staining of extracellular matrix (ECM) components. These scaffolds derived from porcine pancreas were able to maintain the cellular integrity of islets that had repopulated the parenchymal space, which is fundamental for the restoration of endocrine function. Insulin release up to four days after islet infusion was maintained. CONCLUSIONS: This scaffold from a large animal maintained islet survival and function in the short-term, retaining the cells as a solid organ in the parenchymal space after infusion through the pancreatic duct. These results suggest that this scaffold is suitable for further fabrication of fully functional bioengineered endocrine pancreases when implanted in vivo. Therefore, it may represent a key improvement in the field of beta-cell replacement therapy. Nonetheless, the facilitation of longer-term islet survival and studies of implantation in vivo is required for successful clinical translation.
OBJECTIVES: Because therapeutic options for severe diabetes are currently limited, there is a continuing need for new therapeutic strategies, especially in the field of regenerative medicine. Collaborative efforts across the fields of tissue engineering technology and islet biology may be able to create functionally engineered islets capable of restoring endocrine function in patients with insulin-dependent diabetes. METHODS: This engineered scaffold was seeded with isolated primary porcine islets via the pancreatic duct using a multi-step infusion technique. Endocrine function of perfusion-cultured islets in the native scaffold was analyzed by immunohistochemical staining of insulin and glucagon as well as by the insulin stimulation test. RESULTS: The pancreas in this large animal could be uniformly decellularized by perfusion with trypsin and TritonX-100 via the pancreatic duct, as shown by positive staining of extracellular matrix (ECM) components. These scaffolds derived from porcine pancreas were able to maintain the cellular integrity of islets that had repopulated the parenchymal space, which is fundamental for the restoration of endocrine function. Insulin release up to four days after islet infusion was maintained. CONCLUSIONS: This scaffold from a large animal maintained islet survival and function in the short-term, retaining the cells as a solid organ in the parenchymal space after infusion through the pancreatic duct. These results suggest that this scaffold is suitable for further fabrication of fully functional bioengineered endocrine pancreases when implanted in vivo. Therefore, it may represent a key improvement in the field of beta-cell replacement therapy. Nonetheless, the facilitation of longer-term islet survival and studies of implantation in vivo is required for successful clinical translation.
Authors: Clarissa Hernandez Stephens; Kara S Orr; Anthony J Acton; Sarah A Tersey; Raghavendra G Mirmira; Robert V Considine; Sherry L Voytik-Harbin Journal: Am J Physiol Endocrinol Metab Date: 2018-06-12 Impact factor: 4.310
Authors: Roberto Gaetani; Soraya Aude; Lea Lara DeMaddalena; Heinz Strassle; Monika Dzieciatkowska; Matthew Wortham; R Hugh F Bender; Kim-Vy Nguyen-Ngoc; Geert W Schmid-Schöenbein; Steven C George; Christopher C W Hughes; Maike Sander; Kirk C Hansen; Karen L Christman Journal: Tissue Eng Part C Methods Date: 2018-12 Impact factor: 3.056
Authors: Sara Dutton Sackett; Daniel M Tremmel; Fengfei Ma; Austin K Feeney; Rachel M Maguire; Matthew E Brown; Ying Zhou; Xiang Li; Cori O'Brien; Lingjun Li; William J Burlingham; Jon S Odorico Journal: Sci Rep Date: 2018-07-11 Impact factor: 4.379