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Millimeter-thick xenoislet-laden fibers as retrievable transplants mitigate foreign body reactions for long-term glycemic control in diabetic mice.
Biomaterials ( IF 12.8 ) Pub Date : 2020-06-08 , DOI: 10.1016/j.biomaterials.2020.120162
Takaichi Watanabe 1 , Teru Okitsu 1 , Fumisato Ozawa 1 , Shogo Nagata 1 , Hitomi Matsunari 2 , Hiroshi Nagashima 3 , Masaki Nagaya 2 , Hiroki Teramae 1 , Shoji Takeuchi 4
Affiliation  

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.



中文翻译:

作为可移植的移植物,毫米厚的载有异戊二烯的纤维减轻了异物反应,从而可以长期控制糖尿病小鼠的血糖。

如果水凝胶移植通过减轻移植后异物反应获得可恢复性,那么胰岛以及封装在水凝胶中以诱导免疫保护的干细胞衍生的胰岛β细胞的移植技术可以促进治疗1型糖尿病。在这里,我们证明了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及其可回收性。具体来说,我们发现体内当直径大于或等于1.0 mm时,细胞沉积会显着减轻,并且将1.0 mm厚的异种胰岛纤维状水凝胶移植物放置在具有免疫功能的糖尿病小鼠的腹膜腔中100天以上后,即可收回。在此期间,水凝胶移植可以使小鼠的血糖浓度正常化。这些发现可以提供一种创新的移植概念,通过改善其体内功效和安全性来促进干细胞衍生功能细胞的临床应用。

更新日期:2020-06-08
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