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Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model.
Journal of Tissue Engineering ( IF 6.7 ) Pub Date : 2020-05-27 , DOI: 10.1177/2041731420924818
Jordan Magisson 1 , Aladin Sassi 1 , Daela Xhema 2 , Aram Kobalyan 1 , Pierre Gianello 2 , Brice Mourer 3 , Nguyen Tran 3 , Charles-Thibault Burcez 1 , Richard Bou Aoun 1 , Séverine Sigrist 1
Affiliation  

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®. Membranes of MailPan® 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®. 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®. 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® constitutes a promising encapsulation device for widespread use of cell therapy for type 1 diabetes.



中文翻译:

在异基因大鼠模型中新的预先血管化生物人工胰腺的安全性和功能。

细胞封装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和缺氧效率低下的限制。对于这些挑战的回应,我们在体外和体内名为MailPan新巨囊设备的安全性和有效性进行测试®。MailPan的膜®装置在体外在静态条件下进行了测试。在非糖尿病大鼠中植入后评估其生物整合和氧合水平。还用不相容的主要组织相容性复合体在同种异体胰岛装置中注射的大鼠中评估了免疫保护特性。最后,功能糖尿病大鼠与MailPan注入了β细胞系进行评估®。在体外,该装置的膜对葡萄糖,胰岛素和排斥的IgG具有高渗透性。在大鼠中,装置表现出良好的生物整合,高效血管化,和令人满意的充氧(> 5%),而正电子发射断层扫描(PET)〜扫描和血管造影还强调血液循环和MailPan之间快速交换®。该装置通过防止大鼠受体形成针对被包囊的同种异体胰岛的抗体而显示出其免疫保护特性。将大鼠β细胞系注入该设备可正常化糖尿病大鼠的空腹血糖,并在2个月后恢复存活的细胞簇。这些数据表明,MailPan ®构成广泛使用细胞治疗1型糖尿病有前途的封装设备。

更新日期:2020-05-27
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