High-Strength Cell Sheets and Vigorous Hydrogels from Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells

Natural cell derivates, including cell sheets (CSs) andmatrixgels, have opened new opportunities to probe questions in tissue engineeringand regenerative medicine. However, the potential of CSs and hydrogelsgenerated by current protocols is still limited by the challengesof heterogeneity and weak mechanical properties. Here, we developeda 21 day long-term serum-free culture system for human embryonic stemcell (hESC)-derived immunity-and-matrix-regulatory cells (IMRCs).The CSs formed with IMRCs (IMRC-CSs) have a much greater secretioncapacity for the extracellular matrix (ECM) and stronger mechanicalproperties than umbilical cord-derived MSCs, with a ten thousand-foldincrease in elastin, a higher elastic modulus of 1500 kPa, a thickerstructure of 20.59 mu m, and a higher fiber count per square millimeter.The IMRC-CSs could promote corneal chemical injury repair and couldbe turned into injectable temperature-sensitive hydrogels for uterineadhesion repair via a decellularization process. In summary, we haveestablished a high-strength CS platform using human pluripotent stemcells for the first time, providing a facile and scalable engineeringapproach for regenerative medicine.