Evaluation of cardiac automaticity using human cardiac pacemaking cells derived from human embryonic stem/ induced pluripotent stem cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21170
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology; Cardiovascular medicine
• Research Institution: Tottori University
• Principal Investigator: Morikawa Kumi 鳥取大学, 医学部附属病院, 助教 (90707217)
• Co-Investigator(Renkei-kenkyūsha): HISATOME Ichiro 鳥取大学, 医学系研究科, 教授 (60211504) ; SHIRAYOSHI Yasuaki 鳥取大学, 医学系研究科, 准教授 (90249946)
• Research Collaborator: YAZAWA Masayuki
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ペースメーカ細胞 / ヒトES/iPS細胞 / HCN4 / Ifチャネル / 再生医学 / イオンチャネル / 心臓 / 自動能

Outline of Final Research Achievements

Cardiac beating function originates from cardiac pacemaker cells localized in sino-atrial node. The pacemaker cells produce the electrical pulse automatically and lead the contraction of whole heart. However, it is very difficult to isolate the pacemaker cells from human heart directly. To solve this problem, we have developed a novel system for isolating pacemaker cells (HCN4 positive) derived from human embryonic stem /induced pluripotent stem (ES/iPS) cells.
In this study, we have established the dual cardiac fluorescent reporter human ES/iPS cells, in which HCN4 ion-channel and MLC2v myosin light chain gene are knocked-in with eGFP and mCherry, respectively. Electrophysiological analysis indicated that sorted eGFP positive cells showed the same phenotypes as in vivo pacemaker cells on automaticity and If currents. In conclusion, our system provides a useful platform to study the molecular mechanisms underlying cardiac automaticity as well as regenerative medicine for bradycardia.

Free Research Field

心臓分子生理学