Cells And Extracellular Matrices Used In Encapsulation

Successful cell encapsulation involves the choice of the cells to be encapsulated, the type of intracapsular matrix used, and the ability to control membrane geometry, morphology, and transport.[3-9] Cells placed within encapsulation devices generally fall into one of three categories (Table 1) including primary postmitotic cells, immortalized (or dividing) cells, and cell lines that are genetically engineered to produce specific factors. Dividing tissue has advantages over postmitotic tissue; it can be expanded, banked, and thus more easily tested for sterility and contaminants. However, dividing tissue is also constrained by the potential for overgrowth within the capsule environment, resulting in an accumulation of necrotic tissue that could diminish the membrane's

Table 1 Essential components of an immunoisolatory device

Cells Primary

Dividing

Genetically engineered

Extracellular matrix

Hydrogels

Scaffolds

Membranes Dialysis membranes

Polyelectrolytes

Combinations

Islets (diabetes), hepatocytes (liver failure), chromaffin cells (pain and Parkinson's disease) PC12 cells (Parkinson's disease) Fibroblasts producing neurotrophic factors

Alginate and collagen Foamy materials including urethane

PAN-PVC, polysulfone, polyethersulfone Alginate, polylysine, polyornithine

Conformal coating on surface Combined with reinforcing structures permeability characteristics, further reducing cell viability and neurochemical output.

In vivo, extracellular matrices (ECMs) control cell function through the regulation of morphology, proliferation, differentiation, migration, and metastasis. Within a capsule, ECMs are used to prevent aggregation of cells (immobilization) and resultant central necrosis, but are also beneficial to the viability and function of cells that require immobilization. For example, adrenal chromaffin cells have been immobilized in alginate to prevent aggregation and the formation of central necrotic cores. The chromaffin cells thrive in alginate whereas mitot-ically active fibroblasts do not. In this case, the use of alginate is essential to the optimal functioning of this device because some anchorage-dependent cells such as fibroblasts or endothelial cells are present with the adrenal chromaffin cells. In the absence of alginate or similar immobilizing matrices, the fibroblasts expand and overgrow the encapsulated milieu, resulting in a device deficient of bioactive factors produced from the chromaffin cells. In contrast, BHK cells, a fibroblastic cell line, prefer collagen, whereas PC12 cells exhibit a preference for distribution within precipitated chitosan, which provides a scaffolding structure on which the cells anchor.

Polymeric matrices can also be used as cell scaffold material. Poly(ethylene oxide) (PEO)-star copolymers have been fabricated as a potential synthetic extracellular matrix. The star copolymers provide many hydroxyl groups where various synthetic oligopeptides can be attached to desired specifications. Other more resilient polymers such as poly(ethylene terephthalate) (PET) polymers can be extruded into unique geometries which facilitate a three-dimensional arrangement of cells within the device, such as cylinders, braids, or other geometries. Polyesters such as this can be modified to have a surface microtexture for improved cell anchoring or attachment of peptides or other components desirable for cell attachment.

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