A New Bioartificial Pancreas Utilizing Amphiphilic Membranes for the Immunoisolation of Porcine Islets A Pilot Study in the Canine
A New Bioartificial Pancreas Utilizing Amphiphilic Membranes for the Immunoisolation of Porcine Islets A Pilot Study in the Canine
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DOI：
10.1097/mat.0b013e3181a8deba
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发表时间：
2009-07-01
期刊：
影响因子：
4.2
通讯作者：
Kennedy, Joseph P.
中科院分区：
文献类型：
--
作者：
Grundfest-Broniatowski, Sharon F.;Tellioglu, Gurkan;Kennedy, Joseph P.
我们开发了一种可替换的生物人工胰腺，用于治疗糖尿病，利用一种独特的连续的两亲性网状膜，用于猪胰岛细胞(PICs)的大胶囊和免疫隔离。膜由亲水性聚(N，N-二甲基丙烯酰胺)和疏水性/亲氧性聚二甲基硅氧烷链与疏水性/亲氧性聚甲基硅氧烷链交联而成。我们的假设是，这种膜允许异种移植的PIC在没有预血管形成或免疫抑制的情况下存活，因为它具有极高的氧气渗透性和较小的亲水性通道尺寸(3-4 nm)。关键部件是5-10微米厚的半透水两亲性网状膜，膜由含有聚二甲基硅氧烷的聚氨基甲酸酯电纺纳米垫增强，以及提供几何稳定性的激光穿孔镍钛支架。在三只没有免疫抑制的胰腺切除犬身上，加载了PIC，并测试了它们在不发生血管前病变的情况下维持胰岛活性、防止排斥反应和逆转高血糖的能力。组织耐受性好，无全身毒性。该生物人工胰腺在体外和体内都能保护PICS免受有毒环境的伤害。胰岛存活时间长达3周，无排斥迹象。观察新生血管形成情况。高血糖没有逆转，很可能是因为胰岛质量不足。进一步研究以确定胰岛的长期生存能力和纠正高血糖是有必要的。ASAIO期刊2009；55：400-405。
We have developed a replaceable bioartificial pancreas to treat diabetes utilizing a unique cocontinous amphiphilic conetwork membrane created for macroencapsulation and immunoisolation of porcine islet cells (PICs). The membrane is assembled from hydrophilic poly(N,N-dimethyl acrylamide) and hydrophobic/oxyphilic polydimethylsiloxane chains crosslinked with hydrophobic/oxyphilic polymethylhydrosiloxane chains. Our hypothesis is that this membrane allows the survival of xenotransplanted PICs in the absence of prevascularization or immunosuppression because of its extraordinarily high-oxygen permeability and small hydrophilic channel dimensions (3-4 nm). The key components are a 5-10 mu m thick semipermeable amphiphilic conetwork membrane reinforced with an electrospun nanomat of polydimethylsiloxane-containing polyurethane, and a laser-perforated nitinol scaffold to provide geometric stability. Devices were loaded with PICs and tested for their ability to maintain islet viability without prevascularization, prevent rejection, and reverse hyperglycemia in three pancreatectomized dogs without immunosuppression. Tissue tolerance was good and there was no systemic toxicity. The bioartificial pancreas protected PICs from toxic environments in vitro and in vivo. Islets remained viable for up to 3 weeks without signs of rejection. Neovascularization was observed. Hyperglycemia was not reversed, most likely because of insufficient islet mass. Further studies to determine long-term islet viability and correction of hyperglycemia are warranted. ASAIO Journal 2009; 55:400-405.