Engraftment and morphological development of vascularized human iPS cell-derived 3D-cardiomyocyte tissue after xenotransplantation

Abstract

One of the major challenges in cell-based cardiac regenerative medicine is the in vitro construction of three-dimensional (3D) tissues consisting of induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) and a blood vascular network supplying nutrients and oxygen throughout the tissue after implantation. We have successfully built a vascularized iPSC-CM 3D-tissue using our validated cell manipulation technique. In order to evaluate an availability of the 3D-tissue as a biomaterial, functional morphology of the tissues was examined by light and transmission electron microscopy through their implantation into the rat infarcted heart. Before implantation, the tissues showed distinctive myofibrils within iPSC-CMs and capillary-like endothelial tubes, but their profiles were still like immature. In contrast, engraftment of the tissues to the rat heart led the iPSC-CMs and endothelial tubes into organization of cell organelles and junctional apparatuses and prompt development of capillary network harboring host blood supply, respectively. A number of capillaries in the implanted tissues were derived from host vascular bed, whereas the others were likely to be composed by fusion of host and implanted endothelial cells. Thus, our vascularized iPSC-CM 3D-tissues may be a useful regenerative paradigm which will require additional expanded and long-term studies.

Dual Function of iPSC-Derived Pericyte-Like Cells in Vascularization and Fibrosis-Related Cardiac Tissue Remodeling In Vitro

“…Endothelial cells (ECs) have been included in myocardial tissue engineered constructs with the aim of in vitro vascularization; together with stromal cells, they improved the hPSC-derived tissue formation and vascular network growth in matrix-free scaffolds [ 61 ] and in a fibronectin-gelatine matrix [ 62 ].…”

Three‐dimensional bioprinting human cardiac tissue chips of using a painting needle method

“…FN‐G nanofilms were formed onto the cell membranes of isolated hiPSC‐CM and NHCF using a filtration LbL method according to our previous report (Narita et al, ). The cells were suspended in 0.2 mg/ml FN from human plasma (Sigma‐Aldrich, MO) or G (Wako Pure Chemical Industries) in phosphate‐buffered saline (PBS; Wako Pure Chemical Industries), put into a six‐well culture insert with a 3 µm pore membrane (Corning) and shaken for 1 min at 500 rpm using MixMate shaker (Eppendorf).…”

“…In this study, we have constructed 3D cardiac tissues (LbL‐3D Heart) using a LbL cell coating method (Amano et al, ; Narita et al, ; Takeda et al, ) and a microscopic painting device using a painting needle method. Using the painting needle method, the biofabrication device can paint small amounts (several pl to several hundred nl) of bioinks over a wide viscosity range, (1 to 1 × 10 5 mPa·s) quickly (up to once every 0.1 s) and in high resolution.…”

Human-induced pluripotent stem cells derived hematopoietic progenitor cells for treatment of hematopoietic failure among trauma hemorrhagic shock patients

“…7 Currently, iPS-derived cells have been applied for sickle cell anemia, PD, hemophilia A, and acute myocardial infarction in animal models. 8 Recently, Mandai et al reported that administered of iPSC derived retinal pigment epithelial (RPE) cells were used for the treatment of age related macular degeneration (AMD) in human. 9 Recent study suggested that iPSCs-NPCs (Neuronal progenitor cells) have potential efficacy for the treatment of chronic phase of SCI.…”