Cell Sheet-Based Vascularized Myocardial Tissue Fabrication

Abstract

Background: The development of regenerative medicine in recent years has been remarkable as tissue engineering technology and stem cell research have advanced. The ultimate goal of regenerative medicine is to fabricate human organs artificially. If fabricated organs can be transplanted medically, it will be the innovative treatment of diseases for which only donor organ transplantation is the definitive therapeutic method at present. Summary: Our group has reported successful fabrication of thick functional myocardial tissue in vivo and in vitro by using cell sheet engineering technology which requires no scaffolds. Thick myocardial tissue can be fabricated by stacking cardiomyocyte sheets on the vascular bed every 24 h, so that a vascular network can be formed within the myocardial graft. We call this procedure a multi-step transplantation procedure. After human-induced pluripotent stem cells were discovered and human cardiomyocytes became available, a thick, macroscopically pulsate human myocardial tissue was successfully constructed by using a multi-step transplantation procedure. Furthermore, our group succeeded in fabricating functional human myocardial tissue which can generate pressure. Here, we present our way of fabricating human myocardial tissue by means of cell sheet engineering technology. Key Messages: Our group succeeded in fabricating thick, functional human myocardium which can generate pulse pressure. However, there are still a few problems to be solved until clinically functional human cardiac tissue or a whole heart can be fabricated. Research on myocardial regeneration progresses at such a pace that we believe the products of this research will save many lives in the near future.

Drawing Inspiration from Developmental Biology for Cardiac Tissue Engineers

“…[38] As such, many in vitro engineered cardiac tissue models benefit from the inclusion of endothelial cells directly, [45] or at least endothelial-related molecules. [46] Stemcell derived models of co-differentiated cardiac and endothelial cells, [47] cardiac organoid models, [48] spheroid models, [45] and cell sheet-based models [49] have successfully employed endothelial cells in a scaffold-free environment to promote cardiac tissue maturation in vitro. 3D printing has also been used to combine endothelial cells with cardiomyocytes using micro-fibrous hydrogel bioinks.…”

Comparative study of dedifferentiated fat cell and adipose‐derived stromal cell sheets for periodontal tissue regeneration: In vivo and in vitro evidence

“…Cell sheet technology avoids damage to tissue and cells caused by the degraded components of the scaffold material, and is also not affected by the shape of the defect, showing the excellent potential of controllable and directional placement. This technology has been widely used for corneal transplantation, heart repair, and bladder enlargement (Owaki et al, 2014;Iwata et al, 2015;Komae et al, 2018;Li et al, 2019).…”

“…Cell sheet technology avoids damage to tissue and cells caused by the degraded components of the scaffold material, and is also not affected by the shape of the defect, showing the excellent potential of controllable and directional placement. This technology has been widely used for corneal transplantation, heart repair, and bladder enlargement (Owaki et al, 2014; Iwata et al, 2015; Komae et al, 2018; Li et al, 2019). Because of their simple shape, capacity to imitate the cell survival microenvironment, and greater ability to regenerate periodontal tissue, cell sheets are an essential modality for periodontal tissue regeneration.…”