Encapsulated cell grafts to treat cellular deficiencies and dysfunction

Abstract

Cell transplantation provides a therapeutic alternative to whole organ transplantation in the management of diseases arising from the absence or failure of specialized cells. Though allogenic transplantation is favorable in terms of graft acceptance, xenotransplantation can provide a potentially unlimited source of cells and can overcome shortage of human donors. Effective immunoisolation of the xenografts is critical for their long term survival and function. Encapsulation of cells in polymeric matrices, organic or inorganic, provides a physical selectively permeable barrier between the host and the graft, thereby immunoisolating the graft. Microencapsulation of cells in alginate hydrogels has been pervasive, but this approach does not provide precise control over porosity, whereas micro- and nano-fabrication technologies can provide precise and reproducible control over porosity. We highlight both encapsulation approaches in this review, with their relative advantages and challenges. We also highlight the therapeutic potential of encapsulated cells for treating a variety of diseases, detailing the xenotransplantation of pancreatic islets in diabetes therapy as well as the grafting of engineered cells that facilitate localized enzyme-prodrug therapy of pancreatic cancer.

Figure 1

Schematic representation of host immunorejection of cellular grafts, and its prevention through encapsulation. Left panel: Host immune system mediated rejection of transplanted cells through antigen–activated antibody response and through macrophage phagocytosis. Right panel: Immunoprotection of transplanted cells by (a) microencapsulation and (b) macroencapsulation through the physical isolation of the grafts and the prevention of direct contact with the macromolecules of the host immune system. Hydrogel permeability is directed by it’s cross-linking, and is characterized by a wide distribution of pore sizes, whereas nanoelectromechanical systems (NEMS) based microdevices have pore dimensions with nanometer precision.

Figure 2

Scanning electron micrograph of a hydrogel (alginate) microbead.

Figure 3

Confocal fluorescence image of a conformally coated pancreatic islet. Reproduced with kind permission from Ref. . Copyright Wiley-VCH Verlag GmbH & Co. KGaA.

Figure 4

Scanning electron micrograph of nanoporous membranes defined by electron beam lithography (a) and by nanoimprint lithography (b). (a) Reprinted with kind permission from Ref. . Copyright Springer Science+Business Media B.V. (b) Reprinted with kind permission from Ref. . Copyright (2009), American Vacuum Society.