慶應義塾大学 · Biochemistry, Genetics and Molecular Biology
Shugo Tohyama 교수의 연구실은 인간 induced pluripotent stem cells(iPSC)를 활용한 심장 질환 모델링과 심장 재생의학을 핵심으로 삼고 있습니다. 특히, iPSC 유-derived 심근세포와 심장조직을 이용한 3차원 생체모방 조직 공학 기술, 예를 들어 심장 기능을 재현하는 공학적 심장조직(EHT), 심장 기능을 회복시키는 세포 치료, 그리고 약물 독성 평가를 위한 마이크로심장 테스트 모델 개발에 주력하고 있습니다. 연구는 동물 모델(원숭이, 독소)과 인간 세포를 기반으로 한 고도의 정밀한 심장 기능 재현을 목표로 하며, 임상 응용에 이르는 다학제적 접근을 펼치고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The emergence of human induced pluripotent stem cells (hiPSCs) and efficient differentiation of hiPSC-derived cardiomyocytes (hiPSC-CMs) induced from diseased donors have the potential to recapitulate the molecular and functional features of the human heart. Although the immaturity of hiPSC-CMs, including the structure, gene expression, conduct, ion channel density, and Ca 2+ kinetics, is a major challenge, various attempts to promote maturation have been effective. Three-dimensional cardiac mod
We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.
Pigs have traditionally been used for preclinical experiments, and body size-matching is important for cell therapy in animal models used for preclinical trials. It has been shown that the efficacy of the transplanted cells is dependent on the response of the host heart and the age of experimental pigs.
Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular
In vitro reconstruction of highly mature engineered heart tissues (EHTs) is attempted for the selection of cardiotoxic drugs suitable for individual patients before administration. Mechanical contractile force generated in the EHTs is known to be a critical indicator for evaluating the EHT response. However, measuring contractile force requires anchoring the EHT in a tailored force-sensing cell culture chamber, causing technical difficulties in the stable evaluation of contractile force in long-
Three-dimensional (3D) cultures are known to more closely mimic in vivo conditions compared with 2D cultures. Cardiac spheroids (CSs) and organoids (COs) are useful for 3D tissue engineering and are advantageous for their simplicity and mass production for regenerative therapy and drug discovery. Herein, we describe a large-scale method for producing homogeneous human induced pluripotent stem cell (hiPSC)-derived CSs (hiPSC-CSs) and COs without scaffolds using a porous 3D microwell substratum wi
