Production of Cell-Enclosing Microparticles and Microcapsules Using a Water-Immiscible Fluid Under Laminar Flow and Its Applications in Cell Therapy

Reduction in the diameter of cell-enclosing spherical vehicles for cell therapy is an important issue, giving benefits such as higher molecular exchangeability between the enclosed cells and the ambient environment, higher mechanical stability and biocompatibility. In this chapter we review our recent studies for the production of cell-enclosing microparticles and microcapsules of about 100-200 m in diameter. They are much smaller than conventional cell-enclosing spherical vehicles, which are typically between 300 and 1,000 m in diameter. We prepare these small vehicles using droplet breakup through jetting in a water-immiscible liquid stream under laminar flow. Factors for controlling the size of droplets and methods for obtaining gelled vehicles are also described. In addition, we demonstrate the feasibility of these small vehicles for cell therapy by showing the results obtained after implanting the vehicles enclosing cells expressing a cancer-prodrug-converting-enzyme into a mouse with a subcutaneously formed tumor.

Keywords: Microcapsule, cell therapy, co-flowing stream, duplex microcapsule, alginate, agarose, gelatin, horseradish peroxidase, alginate lyase, cross-linking, enzyme, degradation, hollow core, hydrogel membrane, droplets breakup, water-immiscible fluid, alginate with phenolic moieties, hydrogen peroxide, laminar flow, subsieve-size capsule.