5.16 Medical Applications of Cell Sheet Engineering

Abstract

The progress of tissue engineering has been limited by the use of biodegradable scaffolds. New methods are necessary to move the field forward. Cell sheet engineering is a technique for reconstructing tissue with cell sheets harvested from temperature-responsive culture dishes. Temperature-responsive polymers poly( N -isopropylacrylamide) are polymerized and modified on various surfaces, using electron beam radical polymerization. These surfaces can control the attachment and detachment of living cells with temperature changes from 37 to 32 °C. Cultured cells are connected through cell–cell junctional proteins and are harvested as a single cell sheet without using proteolytic enzymes, when the culture temperature is reduced. These cell sheets can be transplanted into the various kinds of tissues without using biodegradable scaffolds. Three-dimensional functional cardiac tissues have been produced using cell sheets. We have succeeded in demonstrating the long-term survival of pulsatile cardiac grafts. Cell sheet patches improve cardiac function in a patient with dilated cardiomyopathy. Cardiac tissue engineering based on cell sheet engineering may prove to be useful for cardiac tissue fabrication and cardiovascular disease therapy. Cell sheet engineering using either two- or three-dimensional cell sheets is recognized to be a useful, fundamental, and generalized technology for next-generation tissue engineering and regenerative medicine.