Wrapping tissues with a pre-established cage-like layer composed of living cells

We report a method for wrapping tissues with a pre-established cage-like layer composed of living cells. We encapsulated multicellular aggregates of human hepatoma HepG2 cells as a model of tissues such as pancreatic islets and hepatocyte spheroids in alginate-based hydrogel microcapsules and subsequently coated the microcapsule surface with a gelatin derivative through a horseradish peroxidase-catalyzed reaction. Human aorta endothelial (HAE) cells grew on the surface and formed a cell layer within 24 h of incubating the microcapsules in a medium containing the cells. Subsequent degradation of the hydrogel microcapsule using a non-proteolytic enzyme, alginate lyase, resulted in a cage-like structure of HAE cells formed around the microcapsule. The HAE cell layer shrank without fragmenting and wrapped the inner spherical tissue. This method was also effective for wrapping multiple cellular aggregates within a single cage of HAE cells. In addition, it was possible to wrap tissue grown from individual cells in spherical cavities within the microcapsules.