Zimmermann H, Zimmermann D, Reuss R, Feilen P J, Manz B, Katsen A, Weber M, Ihmig F R, Ehrhart F, Gessner P, Behringer M, Steinbach A, Wegner L H, Sukhorukov V L, Vásquez J A, Schneider S, Weber M M, Volke F, Wolf R, Zimmermann U
Abteilung Kryobiophysik & Kryotechnologie, Fraunhofer-Institut für Biomedizinische Technik, 66386, St. Ingbert, Germany.
J Mater Sci Mater Med. 2005 Jun;16(6):491-501. doi: 10.1007/s10856-005-0523-2.
The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.
封装细胞疗法的概念非常吸引人，但在实践中，生产长期功能性移植体需要大量的技术和专业知识。藻酸盐是用于同种异体和异种细胞及组织（如朗格汉斯胰岛）免疫隔离的最有前途的生物材料之一。尽管基于藻酸盐的细胞封装已取得了巨大进展，但在考虑常规临床应用之前，仍需进行一些改进。其中之一是生产具有始终如一的高移植级质量的纯化藻酸盐。这在很大程度上取决于输入藻源的纯度以及可验证的藻酸盐提取和纯化工艺的开发。设计基于藻酸盐的免疫隔离微胶囊的一个关键工程挑战是在保持营养物质、氧气和治疗因子（由封装细胞释放）不受阻碍地交换的同时，避免微胶囊肿胀和随后破裂。这需要开发高效、经过验证且有充分记录的用二价阳离子交联藻酸盐的技术。临床应用还需要经过验证的技术来对封装细胞进行长期冷冻保存，以维持产品库存，从而满足最终用户的需求。如此处所示，通过开发用于生产移植级藻酸盐、微胶囊工程和储存的新型经过验证的技术，可以满足这些需求。基于藻酸盐的疗法的进展通过将封装的大鼠和人类胰岛移植到糖尿病小鼠体内得以证明，这些移植体在约1年内正常发挥功能。
