Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model
Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model
复制标题
DOI：
10.1177/2041731420924818
复制
发表时间：
2020-05-01
影响因子：
8.2
通讯作者：
Sigrist, Severine
中科院分区：
文献类型：
--
作者：
Magisson, Jordan;Sassi, Aladin;Sigrist, Severine
细胞包封可以克服游离胰岛移植的局限性，但目前受到细胞免疫保护效率低下和缺氧的限制。为了应对这些挑战，我们在体外和体内测试了一种名为MailPan(R)的新型大胶囊装置的安全性和有效性。在体外静态条件下对MailPan(R)装置的膜进行了检测。在非糖尿病大鼠体内植入后，评估其生物整合和氧合水平。在具有不相容的主要组织相容性复合体的异体胰岛装置中注射大鼠免疫保护性能也被评估。最后，用注射MailPan(R)的β细胞系评估糖尿病大鼠的功能。在体外，该装置的膜对葡萄糖、胰岛素和排斥IgG具有高通透性。在大鼠实验中，该装置表现出良好的生物整合、高效的血管化和良好的氧合（> %），而正电子发射断层扫描（PET）和血管造影也显示了血液循环与MailPan(R)之间的快速交换。该装置通过防止大鼠受体形成针对包封异体胰岛的抗体，显示出其免疫保护特性。将大鼠β细胞系注射到该装置中，使糖尿病大鼠的空腹血糖恢复正常，并在2个月后恢复活细胞团。这些数据表明MailPan(R)是一种有前景的包封装置，可广泛用于1型糖尿病的细胞治疗。
Cell encapsulation could overcome limitations of free islets transplantation but is currently limited by inefficient cells immune protection and hypoxia. As a response to these challenges, we tested in vitro and in vivo the safety and efficacy of a new macroencapsulation device named MailPan(R). Membranes of MailPan(R) device were tested in vitro in static conditions. Its bio-integration and level of oxygenation was assessed after implantation in non-diabetic rats. Immune protection properties were also assessed in rat with injection in the device of allogeneic islets with incompatible Major Histocompatibility Complex. Finally, function was assessed in diabetic rats with a Beta cell line injected in MailPan(R). In vitro, membranes of the device showed high permeability to glucose, insulin, and rejected IgG. In rat, the device displayed good bio-integration, efficient vascularization, and satisfactory oxygenation (>5%), while positron emission tomography (PET)-scan and angiography also highlighted rapid exchanges between blood circulation and the MailPan(R). The device showed its immune protection properties by preventing formation, by the rat recipient, of antibodies against encapsulated allogenic islets. Injection of a rat beta cell line into the device normalized fasting glycemia of diabetic rat with retrieval of viable cell clusters after 2 months. These data suggest that MailPan(R) constitutes a promising encapsulation device for widespread use of cell therapy for type 1 diabetes.