Recent development of temperature-responsive surfaces and their application for cell sheet engineering

Z Tang,T Okano

doi:10.1093/rb/rbu011

Abstract

Cell sheet engineering, which fabricates sheet-like tissues without biodegradable scaffolds, has been proposed as a novel approach for tissue engineering. Cells have been cultured and proliferate to confluence on a temperature-responsive cell culture surface at 37°C. By decreasing temperature to 20°C, an intact cell sheet can be harvested from the culture surface without enzymatic treatment. This new approach enables cells to keep their cell–cell junction, cell surface proteins and extracellular matrix. Therefore, recovered cell sheet can be easily not only transplanted to host tissue, but also constructed a three-dimensional (3D) tissue by layering cell sheets. Moreover, cell sheet manipulation technology and bioreactor have been combined with the cell sheet technology to fabricate a complex and functional 3D tissue in vitro. So far, cell sheet technology has been applied in regenerative medicine for several tissues, and a number of clinical studies have been performed. In this review, recent advances in the preparation of temperature-responsive cell culture surface, the fabrication of organ-like tissue and the clinical application of cell sheet engineering are summarized and discussed.

Highlights

Cell-based regenerative therapy has been developed rapidly as a most promising therapeutic treatment for impaired or defective tissues and organs [1,2,3,4,5,6,7]
The immunoassay of PIPAAm-grafted surface shows that collagen component remains on the surface, though the immunoassay of recovered cell sheet reveals that fibronectin (FN) component is associated with the cell sheet and hardly remains on the surface
These results suggest that the resultant surfaces keep the dehydration of PIPAAm layer without influence of hydrophilic units such as poly(ethylene glycol) (PEG), but achieve a rapid hydration of PIPAAm network due to the freely mobile end of graft PIPAAm chains, resulting in a rapid recovery of cell sheet

Summary

Introduction

Cell-based regenerative therapy has been developed rapidly as a most promising therapeutic treatment for impaired or defective tissues and organs [1,2,3,4,5,6,7]. It is speculated that only several percent of cultured cells are transplanted to target tissues, which significantly reduces the expected therapeutic effects [9]. To resolve these problems, in 1993, Langer and Vacanti [10] proposed the tissue engineering approach as the second generation of cell-based therapy. By reducing temperature from 37C to 20C, cultured cells can be harvested as an intact contiguous cell sheet, and transplanted to host tissue. This approach called as ‘cell sheet engineering’. Similar as EB irradiation, plasma and ultra violet (UV) irradiation are used as an alternative approach to prepare PIPAAm-grafted

Modification procedure

Findings

Conclusion