RRC ID 45435
Author Komae H, Sekine H, Dobashi I, Matsuura K, Ono M, Okano T, Shimizu T.
Title Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells.
Journal J Tissue Eng Regen Med
Abstract The most radical treatment currently available for severe heart failure is heart transplantation; however, the number of donor hearts is limited. A better approach is to make human cardiac tissues. We developed an original cell sheet-based tissue-engineering technology to fabricate human cardiac tissue by layering myocardial cell sheets. Human induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes to fabricate cardiomyocyte sheets. Initially, three-layer human iPS cardiomyocyte (hiPSCM) sheets were transplanted on subcutaneous tissues of nude rats. Next, to fabricate thicker tissue, three-layer sheets were transplanted on one day, then additional three-layer sheets were transplanted onto them the following day, after the first sheets were vascularized. On day 3, the final three-layer sheets were again transplanted, creating a nine-layer graft (multi-step transplantation procedure). In the last step, six-layer sheets were transplanted on fat tissues of the inguinal portion, which were subsequently resected together with the femoral arteries and veins to make transplantable grafts with connectable vessels. They were then transplanted ectopically to the neck portion of other rats by anastomosing vessels with the host's jugular arteries and veins. Transplanted three-layer hiPSCMs were beating and, histologically, showed a cardiac muscle-like structure with vascular systems. Moreover, transplanted hiPSCMs proliferated and matured in vivo. Significantly thicker tissues were fabricated by a multi-step transplantation procedure. The ectopically transplanted graft survived and continued to beat. We succeeded in fabricating functional human cardiac tissue with cell sheet technology. Transplanting this cardiac tissue may become a new treatment option for severe heart failure. Copyright © 2015 John Wiley & Sons, Ltd.
Volume 11(3)
Pages 926-935
Published 2017-3-1
DOI 10.1002/term.1995
PMID 25628251
MeSH Animals Cell Proliferation Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / transplantation Induced Pluripotent Stem Cells / ultrastructure Male Myocardium / cytology* Neovascularization, Physiologic Rats, Inbred F344 Rats, Nude
IF 3.319
Times Cited 27
Human and Animal Cells 253G1(HPS0002)