Oligomeric collagen as an encapsulation material for islet/β-cell replacement: effect of islet source, dose, implant site, and administration format.
Oligomeric collagen as an encapsulation material for islet/β-cell replacement: effect of islet source, dose, implant site, and administration format.
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寡聚胶原蛋白作为胰岛/β 细胞替代的封装材料：胰岛来源、剂量、植入部位和给药方式的影响。
DOI：
10.1152/ajpendo.00066.2020
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Voytik-Harbin,Sherry
中科院分区：
文献类型：
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作者：
Stephens,ClarissaHernandez;Morrison,RachelA;McLaughlin,Madeline;Orr,Kara;Tersey,SarahA;Scott-Moncrieff,JCatharine;Mirmira,RaghavendraG;Considine,RobertV;Voytik-Harbin,Sherry
更换提供持久葡萄糖感应和胰岛素释放功能的胰岛/β细胞有可能恢复 1 型糖尿病患者的长期血糖控制。不幸的是，持续的挑战阻碍了此类疗法在临床上的广泛应用，包括通过门静脉输注给药的繁琐、给药后功能性胰岛质量的显着损失、功能寿命有限以及需要全身免疫抑制。此前，纤维形成 I 型胶原蛋白（寡聚物）被证明可以支持糖尿病小鼠皮下注射和原位封装同基因胰岛，快速（<24 小时）逆转高血糖并维持正常血糖超过 90 天。在这里，我们进一步评估了这种宏观封装策略，定义了胰岛来源（同种异体和异种）和剂量（500和800个胰岛）、注射微环境（皮下和腹膜内）以及大胶囊形式（可注射和预成型植入）对胰岛功能寿命和受体免疫反应的影响。我们发现异种大鼠胰岛的功能与同种异体小鼠胰岛相似或更好，但随着剂量的增加，寿命仅略有改善。此外，与腹膜内给药相比，皮下注射可带来更一致的包封结果，并改善胰岛健康和寿命，而皮下注射和预制植入形式之间没有观察到显着差异。总的来说，这些结果证明了将天然胶原蛋白纳入胰岛/β细胞替代疗法的好处。
Replacement of islets/β-cells that provide long-lasting glucose-sensing and insulin-releasing functions has the potential to restore extended glycemic control in individuals with type 1 diabetes. Unfortunately, persistent challenges preclude such therapies from widespread clinical use, including cumbersome administration via portal vein infusion, significant loss of functional islet mass upon administration, limited functional longevity, and requirement for systemic immunosuppression. Previously, fibril-forming type I collagen (oligomer) was shown to support subcutaneous injection and in situ encapsulation of syngeneic islets within diabetic mice, with rapid (<24 h) reversal of hyperglycemia and maintenance of euglycemia for beyond 90 days. Here, we further evaluated this macroencapsulation strategy, defining effects of islet source (allogeneic and xenogeneic) and dose (500 and 800 islets), injection microenvironment (subcutaneous and intraperitoneal), and macrocapsule format (injectable and preformed implantable) on islet functional longevity and recipient immune response. We found that xenogeneic rat islets functioned similarly to or better than allogeneic mouse islets, with only modest improvements in longevity noted with dosage. Additionally, subcutaneous injection led to more consistent encapsulation outcomes along with improved islet health and longevity, compared with intraperitoneal administration, whereas no significant differences were observed between subcutaneous injectable and preformed implantable formats. Collectively, these results document the benefits of incorporating natural collagen for islet/β-cell replacement therapies.