Teotia Rohit S, Kadam Sachin, Singh Atul Kumar, Verma Surendra Kumar, Bahulekar Ashutosh, Kanetkar Sujata, Bellare Jayesh
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400079, Maharashtra, India.
Krishna Institute of Medical Science University, Malkapur, Karad (Dist.Satara) 415110, Maharashtra, India.
Mater Sci Eng C Mater Biol Appl. 2017 Aug 1;77:857-866. doi: 10.1016/j.msec.2017.04.003. Epub 2017 Apr 3.
Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose. Important structural variables such as fiber material, dope composition, dimensions, surface characteristics etc., were precisely engineered and tuned for bioartificial pancreas application. The HFMs were characterized for their morphology, molecular diffusion, selectivity and protein absorption. The optimized Polysulfone(Psf)/TPGS composite HFMs, which contained TPGS, exhibited uniformed structure with low insulin adsorption and high permeability of insulin. The HFM was further studied for the encapsulation and in-vitro growth with porcine and differentiated islets isolated from human umbilical cord Wharton's jelly. To prove their efficacy under in-vivo conditions, the Polysulfone(Psf)/TPGS composite HFMs were encapsulated with either of these isolated cells (porcine islets or islet like cell clusters derived from mesenchymal stem cells isolated from human umbilical cord Wharton's jelly) and they were transplanted in experimental STZ induced diabetic mice. The results showed restoration of normoglycemia for 30days, indicating their ability to respond efficiently to high glucose without immune-rejection. Thus, these results indicate that Polysulfone (Psf)/TPGS composite HFMs can be used as an implantable, immune-competent bioartificial pancreas as a therapy for type 1 diabetes.
来自异种来源的胰岛以及源自自体干细胞的胰岛样簇已成为用于治疗1型糖尿病的尸体胰腺的替代物。然而，将这些胰岛与宿主免疫系统进行免疫隔离存在生物相容性和缺氧问题。为了克服免疫屏障生物相容性问题，我们使用专门为此开发的中空纤维纺丝中试装置，研制了一种聚砜（Psf）/TPGS复合中空纤维膜（HFM）。针对生物人工胰腺应用，对纤维材料、纺丝液组成、尺寸、表面特性等重要结构变量进行了精确设计和调整。对这些中空纤维膜的形态、分子扩散、选择性和蛋白质吸附进行了表征。优化后的含有TPGS的聚砜（Psf）/TPGS复合中空纤维膜呈现出均匀的结构，胰岛素吸附量低且胰岛素通透性高。进一步研究了该中空纤维膜对猪胰岛以及从人脐带华通氏胶中分离出的分化胰岛的包封和体外生长情况。为了证明其在体内条件下的疗效，将聚砜（Psf）/TPGS复合中空纤维膜用这些分离出的细胞（猪胰岛或从人脐带华通氏胶中分离出的间充质干细胞衍生的胰岛样细胞簇）中的任一种进行包封，然后移植到实验性链脲佐菌素诱导的糖尿病小鼠体内。结果显示血糖正常恢复了30天，表明它们能够在无免疫排斥的情况下有效应对高血糖。因此，这些结果表明聚砜（Psf）/TPGS复合中空纤维膜可作为一种可植入的、具有免疫活性的生物人工胰腺用于1型糖尿病的治疗。
