Therapeutic uses of microencapsulated genetically engineered cells
Section snippets
Principles of action of microcapsules
Biologically active materials retained inside microcapsules can act on smaller molecules that can diffuse across the membrane of the microcapsule from the outside (Fig. 1). Small molecules produced inside the microcapsules can also diffuse across the membrane into the `extracellular' environment.
A further advantage of microcapsules is that the capsule contents are protected from immune rejection because leukocytes and antibodies cannot penetrate the capsule2, 3, 4(Fig. 1). This allows
The evolution of microcapsule technology
The first semipermeable microcapsules contained hemoglobin (for use as a blood substitute), enzymes (to treat inborn errors of metabolism) or adsorbents (to treat drug overdoses) and were of cellular dimensions (in the micrometer range)1, 2, 3, 4. They were composed of semipermeable polymers such as cellulose nitrate or polyamide, or of crosslinked protein membranes1, 2(Fig. 2). This was followed by the use of silastic—a polymer that is permeable only to lipophilic molecules (Fig. 2). To allow
Implantation of microencapsulated genetically engineered cells
Genetic engineering has made it possible to develop microcapsules that are much more efficient than any of the biologically active materials used in the first-generation artificial cells (reviewed in Ref. [6]). Some examples of the types of genetically engineered, microencapsulated cells used to treat a range of diseases are given in Table 1 (Refs 12, 13, 14, 15, 16, 17, 18, 19). The promising results obtained so far have stimulated further research into the safety and long-term feasibility of
Oral administration of microencapsulated genetically engineered cells
An exciting development is our recent finding that orally administered artificial cells might be suitable for some applications. Orally administered microcapsules avoid the need for implantation24, 25, 26, and therefore obviate many of the problems associated with this approach. During the passage of microcapsules through the gastrointestinal tract, small molecules (such as urea, ammonia or amino acids) from the body enter the microcapsules where they can be metabolized by genetically
Different strategies for different diseases
Long-term implantation of microencapsulated genetically engineered cells for a variety of conditions will probably take several years to perfect. Meanwhile, several groups are looking into other configurations for more immediate clinical application. For example, Aebischer's ingenious use of capillary fibers to encapsulate cells has allowed his group to insert these subcutaneously into the cerebrospinal fluid on a short-term basis[30]. This allows the capsules to be replaced when necessary[30],
Glossary
Alginate–polylysine–alginate—Membrane formed by the interaction of alginate, an anionic gel, with polylysine, a polycation.
Allogeneic—From an unrelated member of the same species.
Hemoperfusion—The process by which a patient's blood is perfused through a column of biologically active particles then returned to the patient.
Semipermeable microcapsules—Microscopic containers enclosing biologically active materials. The encapsulating membrane retains the contents but allows smaller molecules to
The outstanding questions
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Which other conditions could be treated using oral therapy with microencapsulated cells?
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Will a combination of microencapsulated E. coli DH5 cells (to remove urea) and oral adsorbents and osmotic agents (to control water, electrolytes and other uremic waste metabolites) remove the need for dialysis in patients with kidney failure?
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What is the role of complement components and cytokines in the long-term function of implanted, microencapsulated genetically engineered cells?
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How can the tissue
Acknowledgements
T.M.S.C. acknowledges the grant support and career investigatorship from the Medical Research Council of Canada and the `Virage' Center of Excellence Award from the Quebec Ministry of Higher Education, Science and Technology.
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Cited by (102)
Polymeric carriers for enhanced delivery of probiotics
2020, Advanced Drug Delivery ReviewsCitation Excerpt :An example for reverse lectin targeting, is development of colon-targeted delivery systems based on the reverse lectin targeting of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated WGA and PNA [53]. In this example, WGA is wheat germ agglutinin and PNA is peanut agglutinin that binds to N-acetyl-D-glucosamine and α-lactose as the carbohydrates, respectively [53]. Lectins are classified to plant lectins and animal lectins and each type of these lectins has different specific interactions with carbohydrates.
3D cell-laden polymers to release bioactive products in the eye
2019, Progress in Retinal and Eye ResearchCitation Excerpt :Thanks to the intrinsic characteristics of this membrane, nutrients and oxygen are able to penetrate the core, while the waste and therapeutic products of interest are released. In contrast, T-cell receptors and immunoglobulins are not able to interact with surface antigens on protected cells, and even access of the complement system is partially prevented by membrane pores; thereby avoiding or at least reducing their cytotoxic activity (Fig. 3) (Chang and Prakash, 1998). The outer coatings are primarily responsible for mechanical properties of microcapsules, providing resistance to either pressures exerted by the nearby tissues or pressures generated by enclosed cells because of possible overgrowth.
Mimicking oxygen delivery and waste removal functions of blood
2017, Advanced Drug Delivery ReviewsCitation Excerpt :Encapsulated activated charcoal has been used to replace some of the kidney’s function to remove nitrogen metabolites and has been found improve the kidney function of rats with chronic renal failure [405,416]. Microencapsulated genetically transfected cells have been used to remove urea and successfully reduce plasma urea levels in uremic rats by oral administration [452,453]. Researchers have found that incorporation of renal tubule cells into filtering fibers improves ammonia excretion in uremic dogs [454].
Magnetic nanoparticle hyperthermia induced cytosine deaminase expression in microencapsulated E. coli for enzyme-prodrug therapy
2015, Journal of BiotechnologyCitation Excerpt :Clinical applications of alginate microcapsules has included the transplantation of pancreatic islets, from both autologous and non-autologous sources, for the treatment of type 1 diabetes mellitus (Zimmermann et al., 2007). Alginate microcapsules have also been used in the delivery of live therapeutic bacteria (Chang and Prakash, 1998). While encapsulation of cytosine deaminase producing E. coli in alginate microcapsules addresses the issues of immunogenicity and long term enzyme stability, the therapeutic utility of encapsulated cells is dependent upon controlled induction of cytosine deaminase expression.
Artificial Cells
2013, Biomaterials Science: An Introduction to Materials: Third EditionStem cell technology for the treatment of acute and chronic renal failure
2010, Translational Research
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