Generation of murine cardiac pacemaker cell aggregates based on ES-cell-programming in combination with Myh6-promoter-selection.
J Vis Exp
; (96): e52465, 2015 Feb 17.
Article
em En
| MEDLINE
| ID: mdl-25742394
ABSTRACT
Treatment of the "sick sinus syndrome" is based on artificial pacemakers. These bear hazards such as battery failure and infections. Moreover, they lack hormone responsiveness and the overall procedure is cost-intensive. "Biological pacemakers" generated from PSCs may become an alternative, yet the typical content of pacemaker cells in Embryoid Bodies (EBs) is extremely low. The described protocol combines "forward programming" of murine PSCs via the sinus node inducer TBX3 with Myh6-promoter based antibiotic selection. This yields cardiomyocyte aggregates consistent of >80% physiologically functional pacemaker cells. These "induced-sinoatrial-bodies" ("iSABs") are spontaneously contracting at yet unreached frequencies (400-500 bpm) corresponding to nodal cells isolated from mouse hearts and are able to pace murine myocardium ex vivo. Using the described protocol highly pure sinus nodal single cells can be generated which e.g. can be used for in vitro drug testing. Furthermore, the iSABs generated according to this protocol may become a crucial step towards heart tissue engineering.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nó Sinoatrial
/
Proteínas com Domínio T
/
Células-Tronco Pluripotentes
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article