Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes.
نویسندگان
چکیده
Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca2+-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.
منابع مشابه
O-5: Preparation of Multi-Component Drug Delivery Systems
Background: Despite global interest, the development of single step processes for the preparation of effective drug delivery systems still faces numerous challenges. There is great demand for processing methods that are efficient, flexible, scalable and economical for the generation of wide range of encapsulated structures. Over the past few decades, electrohydrodynamic (EHD) processing has rec...
متن کاملDesigning an Engineered Construct Gene Sensitive to Carbohydrate In-vitro and Candidate for Human Insulin Gene Therapy In-vivo
Background and Aim: Diabetes is a common disorder worldwide, and exhaustive efforts have been made to cure this disease. Gene therapy has considered as a potential curative method that has more stability in comparison with the other pharmaceutical methods. However, the application of gene therapy as a definitive treatment demands further investigation. This study aim is to prepare a suitable hi...
متن کاملDesigning an Engineered Construct Gene Sensitive to Carbohydrate In-vitro and Candidate for Human Insulin Gene Therapy In-vivo
Background and Aim: Diabetes is a common disorder worldwide, and exhaustive efforts have been made to cure this disease. Gene therapy has considered as a potential curative method that has more stability in comparison with the other pharmaceutical methods. However, the application of gene therapy as a definitive treatment demands further investigation. This study aim is to prepare a suitable hi...
متن کاملSynthesis of Metformin Hydrochloride nanoliposomes: Evaluation of physicochemical characteristics and release kinetics
Metformin hydrochloride, a drug group of biguanides, with significant efficacy in the treatment of diabetes type II, is decomposed before reaching to the stomach and is wasted in great losses. In this study, the nanoliposomes of metformin hydrochloride were prepared with Bingham method. At first, the single factor test is done. Design variables are: lecithin to cholesterol ratio, organic solven...
متن کاملSynthesis of Metformin Hydrochloride nanoliposomes: Evaluation of physicochemical characteristics and release kinetics
Metformin hydrochloride, a drug group of biguanides, with significant efficacy in the treatment of diabetes type II, is decomposed before reaching to the stomach and is wasted in great losses. In this study, the nanoliposomes of metformin hydrochloride were prepared with Bingham method. At first, the single factor test is done. Design variables are: lecithin to cholesterol ratio, organic solven...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 115 2 شماره
صفحات -
تاریخ انتشار 2018