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

Abstract

Natural cell derivates, including cell sheets (CSs) and matrix gels, have opened new opportunities to probe questions in tissue engineering and regenerative medicine. However, the potential of CSs and hydrogels generated by current protocols is still limited by the challenges of heterogeneity and weak mechanical properties. Here, we developed a 21 day long-term serum-free culture system for human embryonic stem cell (hESC)-derived immunity-and-matrix-regulatory cells (IMRCs). The CSs formed with IMRCs (IMRC-CSs) have a much greater secretion capacity for the extracellular matrix (ECM) and stronger mechanical properties than umbilical cord-derived MSCs, with a ten thousand-fold increase in elastin, a higher elastic modulus of 1500 kPa, a thicker structure of 20.59 μm, and a higher fiber count per square millimeter. The IMRC-CSs could promote corneal chemical injury repair and could be turned into injectable temperature-sensitive hydrogels for uterine adhesion repair via a decellularization process. In summary, we have established a high-strength CS platform using human pluripotent stem cells for the first time, providing a facile and scalable engineering approach for regenerative medicine.

Cornea-Specific Human Adipose Stem Cell-Derived Extracellular Matrix for Corneal Stroma Tissue Engineering

“…In our study, we noted that the ECM sheet exhibited favorable properties for handling, cutting, and transfer, even after rigorous processing such as vortexing. The resilience was particularly noteworthy as cell-derived sheets often lack mechanical strength due to insufficient thickness. ,, Interestingly, ECM sheets hold significant promise for TE and regenerative medicine applications, potentially serving as a therapeutic option for corneal injuries during wound healing. While hASC-derived ECM sheets have been explored for skin substitutes in wound healing, , the production of ECM sheet during the differentiation of hASCs toward CSKs is a novel approach.…”

“…Three-dimensional (3D) bioprinting is a state-of-the-art biofabrication technology to manufacture 3D tissue constructs with precise cellular architecture and addresses the substantial need for transplantable tissues and organs. , Therefore, it has gained popularity also in fabricating corneal stromal structures. − Previously cornea-specific bioinks have been prepared by using ECM from donor tissue, such as bovine or porcine corneas . Furthermore, cell-derived ECM for corneal TE has been studied with corneal endothelial cells (CECs) as a culture substrate, a corneal endothelium graft, as a model to study cellular dysfunction, or in applications for corneal injury repair. − …”

iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review

“…Until recently, pluripotent cell-derived MSCs were not a popular focus in clinical research, with only a small number of studies exploring this area, despite the wide variety of potential tissues that could be produced. Currently, only three clinical trials involving ESC-derived MSCs [ 81 – 83 ], and six iPSC-MSCs clinical trials have been reported (Table 2 ) [ 84 , 85 ]. It is important to note that from the six clinical trials, cartilage regeneration through iPSC-MSCs was only addressed in two studies.…”