Watanabe Takaichi, Okitsu Teru, Ozawa Fumisato, Nagata Shogo, Matsunari Hitomi, Nagashima Hiroshi, Nagaya Masaki, Teramae Hiroki, Takeuchi Shoji
Institute of Industrial Science (IIS), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.
Meiji University International Institute for Bio-Resource Research, Kawasaki, 214-8571, Japan.
Biomaterials. 2020 Oct;255:120162. doi: 10.1016/j.biomaterials.2020.120162. Epub 2020 Jun 8.
Transplantation technologies of pancreatic islets as well as stem cell-derived pancreatic beta cells encapsulated in hydrogel for the induction of immunoprotection could advance to treat type 1 diabetes mellitus, if the hydrogel transplants acquire retrievability through mitigating foreign body reactions after transplantation. Here, we demonstrate that the diameter of the fiber-shaped hydrogel transplants determines both in vivo cellular deposition onto themselves and their retrievability. Specifically, we found that the in vivo cellular deposition is significantly mitigated when the diameter is 1.0 mm and larger, and that 1.0 mm-thick xenoislet-laden fiber-shaped hydrogel transplants can be retrieved after being placed in the intraperitoneal cavities of immunocompetent diabetic mice for more than 100 days, during which period the hydrogel transplants can normalize the blood glucose concentrations of the mice. These findings could provide an innovative concept of a transplant that would promote the clinical application of stem cell-derived functional cells through improving their in vivo efficacy and safety.
如果水凝胶移植物通过减轻移植后的异物反应而具备可回收性，那么胰岛移植技术以及包裹在水凝胶中的干细胞来源的胰腺β细胞用于诱导免疫保护，可能会推动1型糖尿病的治疗。在此，我们证明纤维状水凝胶移植物的直径决定了体内细胞在其自身上的沉积以及它们的可回收性。具体而言，我们发现当直径为1.0毫米及更大时，体内细胞沉积会显著减轻，并且载有异种胰岛的1.0毫米厚纤维状水凝胶移植物在置于免疫活性糖尿病小鼠的腹腔中超过100天后可以被回收，在此期间水凝胶移植物可使小鼠的血糖浓度正常化。这些发现可能会提供一种移植的创新概念，即通过提高其体内功效和安全性来促进干细胞来源的功能细胞的临床应用。
