Cell encapsulation

Cell microencapsulation technology involves immobilization of the cells within a polymeric semi-permeable membrane that permits the bidirectional diffusion of molecules such as the influx of oxygen, nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products and therapeutic proteins. At the same time, the semi-permeable nature of the membrane prevents immune cells and antibodies from destroying the encapsulated cells regarding them as foreign invaders. Cell microencapsulation technology involves immobilization of the cells within a polymeric semi-permeable membrane that permits the bidirectional diffusion of molecules such as the influx of oxygen, nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products and therapeutic proteins. At the same time, the semi-permeable nature of the membrane prevents immune cells and antibodies from destroying the encapsulated cells regarding them as foreign invaders. The main motive of cell encapsulation technology is to overcome the existing problem of graft rejection in tissue engineering applications and thus reduce the need for long-term use of immunosuppressive drugs after an organ transplant to control side effects. In 1933 Vincenzo Bisceglie made the first attempt to encapsulate cells in polymer membranes. He demonstrated that tumor cells in a polymer structure transplanted into pig abdominal cavity remained viable for a long period without being rejected by the immune system. Thirty years later in 1964, the idea of encapsulating cells within ultra thin polymer membrane microcapsules so as to provide immunoprotection to the cells was then proposed by Thomas Chang who introduced the term 'artificial cells' to define this concept of bioencapsulation. He suggested that these artificial cells produced by a drop method not only protected the encapsulated cells from immunorejection but also provided a high surface-to-volume relationship enabling good mass transfer of oxygen and nutrients.Twenty years later, this approach was successfully put into practice in small animal models when alginate-polylysine-alginate (APA) microcapsules immobilizing xenograft islet cells were developed. The study demonstrated that when these microencapsulated islets were implanted into diabetic rats, the cells remained viable and controlled glucose levels for several weeks.Human trials utilising encapsulated cells were performed in 1998. Encapsulated cells expressing a cytochrome P450 enzyme to locally activate an anti-tumour prodrug were used in a trial for advanced, non-resectable pancreatic cancer. Approximately a doubling of survival time compared to historic controls was demonstrated. Questions could arise as to why the technique of encapsulation of cells is even required when therapeutic products could just be injected at the site. An important reason for this is that the encapsulated cells would provide a source of sustained continuous release of therapeutic products for longer durations at the site of implantation. Another advantage of cell microencapsulation technology is that it allows the loading of non-human and genetically modified cells into the polymer matrix when the availability of donor cells is limited. Microencapsulation is a valuable technique for local, regional and oral delivery of therapeutic products as it can be implanted into numerous tissue types and organs. For prolonged drug delivery to the treatment site, implantation of these drug loaded artificial cells would be more cost effective in comparison to direct drug delivery. Moreover, the prospect of implanting artificial cells with similar chemical composition in several patients irrespective of their leukocyte antigen could again allow reduction in costs. The potential of using cell microencapsulation in successful clinical applications can be realized only if several requirements encountered during the development process are optimized such as the use of an appropriate biocompatible polymer to form the mechanically and chemically stable semi-permeable matrix, production of uniformly sized microcapsules, use of an appropriate immune-compatible polycations cross-linked to the encapsulation polymer to stabilized the capsules, selection of a suitable cell type depending on the situation. The use of the best biomaterial depending on the application is crucial in the development of drug delivery systems and tissue engineering. The polymer alginate is very commonly used due to its early discovery, easy availability and low cost but other materials such as cellulose sulphate, collagen, chitosan, gelatin and agarose have also been employed. Several groups have extensively studied several natural and synthetic polymers with the goal of developing the most suitable biomaterial for cell microencapsulation. Extensive work has been done using alginates which are regarded as the most suitable biomaterials for cell microencapsulation due to their abundance, excellent biocompatibility and biodegradability properties. Alginate is a natural polymer which can be extracted from seaweed and bacteria with numerous compositions based on the isolation source. Alginate is not free from all criticism. Some researchers believe that alginates with high-M content could produce an inflammatory response and an abnormal cell growth while some have demonstrated that alginate with high-G content lead to an even higher cell overgrowth and inflammatory reaction in vivo as compared to intermediate-G alginates.Even ultrapure alginates may contain endotoxins, and polyphenols which could compromise the biocompatibility of the resultant cell microcapsules. It has been shown that even though purification processes successfully lower endotoxin and polyphenol content in the processed alginate, it is difficult to lower the protein content and the purification processes could in turn modify the properties of the biomaterial. Thus it is essential that an effective purification process is designed so as to remove all the contaminants from alginate before it can be successfully used in clinical applications.