Differentiation of rat embryonic stem cells into functional cardiomyocytes

摘要

Rats(Rattus norvegicus) have many advantages over mice in scientific studies,for example, they are more relevant to human in physiological and pharmacological responses.Therefore,rats are broadly used in experimental studies.The recent breakthrough in the generation of rat embryonic stem cells(rESCs) opens the door to application of gene targeting to create models for the study of human diseases.In addition,the in vitro differentiation of rESCs into derivatives of three germ lines will serve as a powerful tool and resource for the investigation of mammalian development,cell function, tissue repair,and drug discovery.However, the distinct culture condition and signal inhibitor-depended maintenance of rESCs stand as a considerable challenge for its in vitro differentiation.To address it,we investigated whether rESCs are capable of forming terminal differentiated cardiomyocytes. We found that the embryoid bodies(EBs)-based method used in mouse ESC(mESC) differentiation failed to work in the cultivation of rESCs.We then modified the differentiation protocol and successfully developed an in vitro differentiation system to differentiate rESCs into three embryonic germ layers.By using this method,the rESCs form spontaneous beating cardiomyocytes with the properties similar to those derived from fetal rat hearts and mESCs.This unique cellular system will provide a new approach to study the early development and cardiac function as well as to perform pharmacological test and cell therapy study(Grants:the State Major Research Program of China(2009ZX09503-024,2010CB945603) and CAS(XDA01030000).