PMID- 24936448
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20211124
IS  - 2213-6711 (Print)
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 2
IP  - 5
DP  - 2014 May 6
TI  - Programming and isolation of highly pure physiologically and pharmacologically 
      functional sinus-nodal bodies from pluripotent stem cells.
PG  - 592-605
LID - 10.1016/j.stemcr.2014.03.006 [doi]
AB  - Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers, 
      which lack hormone responsiveness and bear hazards such as infection and battery 
      failure. These issues may be overcome via "biological pacemakers" derived from 
      pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs 
      with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based 
      antibiotic selection leads to cardiomyocyte aggregates consisting of >80% 
      physiologically and pharmacologically functional pacemaker cells. These induced 
      sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm), 
      coming close to those found in mouse hearts, and were able to robustly pace 
      myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal 
      tissue that is derived from PSCs and may be important for future cell therapies 
      and drug testing in vitro.
FAU - Jung, Julia Jeannine
AU  - Jung JJ
AD  - Referenz und Translationszentrum fur Kardiale Stammzelltherapie (RTC) der 
      Universitat Rostock, 18057 Rostock, Germany.
FAU - Husse, Britta
AU  - Husse B
AD  - Universitatsklinik fur Innere Medizin III, Kardiologie und Angiologie, 6020 
      Innsbruck, Austria ; Walter Brendel Centre, LMU Munich, 81377 Munich, Germany.
FAU - Rimmbach, Christian
AU  - Rimmbach C
AD  - Referenz und Translationszentrum fur Kardiale Stammzelltherapie (RTC) der 
      Universitat Rostock, 18057 Rostock, Germany.
FAU - Krebs, Stefan
AU  - Krebs S
AD  - Gene Center Munich, LMU Munich, 81377 Munich, Germany.
FAU - Stieber, Juliane
AU  - Stieber J
AD  - Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie der FAU 
      Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Steinhoff, Gustav
AU  - Steinhoff G
AD  - Referenz und Translationszentrum fur Kardiale Stammzelltherapie (RTC) der 
      Universitat Rostock, 18057 Rostock, Germany.
FAU - Dendorfer, Andreas
AU  - Dendorfer A
AD  - Walter Brendel Centre, LMU Munich, 81377 Munich, Germany ; German Center for 
      Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, 
      Germany.
FAU - Franz, Wolfgang-Michael
AU  - Franz WM
AD  - Universitatsklinik fur Innere Medizin III, Kardiologie und Angiologie, 6020 
      Innsbruck, Austria.
FAU - David, Robert
AU  - David R
AD  - Referenz und Translationszentrum fur Kardiale Stammzelltherapie (RTC) der 
      Universitat Rostock, 18057 Rostock, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140417
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
RN  - 0 (Myh6 protein, mouse)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (Tbx3 protein, mouse)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Biological Clocks
MH  - Calcium/metabolism
MH  - Cell Differentiation
MH  - Cell Line
MH  - *Cellular Reprogramming
MH  - Coculture Techniques
MH  - In Vitro Techniques
MH  - Mice
MH  - Models, Biological
MH  - Myocytes, Cardiac/metabolism
MH  - Myosin Heavy Chains/genetics/metabolism
MH  - Patch-Clamp Techniques
MH  - Pluripotent Stem Cells/*cytology/metabolism
MH  - Sick Sinus Syndrome/metabolism/pathology/veterinary
MH  - Sinoatrial Node/cytology/*physiology
MH  - T-Box Domain Proteins/genetics/metabolism
PMC - PMC4050488
EDAT- 2014/06/18 06:00
MHDA- 2014/06/18 06:01
PMCR- 2014/04/17
CRDT- 2014/06/18 06:00
PHST- 2014/02/28 00:00 [received]
PHST- 2014/03/17 00:00 [revised]
PHST- 2014/03/18 00:00 [accepted]
PHST- 2014/06/18 06:00 [entrez]
PHST- 2014/06/18 06:00 [pubmed]
PHST- 2014/06/18 06:01 [medline]
PHST- 2014/04/17 00:00 [pmc-release]
AID - S2213-6711(14)00085-X [pii]
AID - 10.1016/j.stemcr.2014.03.006 [doi]
PST - epublish
SO  - Stem Cell Reports. 2014 Apr 17;2(5):592-605. doi: 10.1016/j.stemcr.2014.03.006. 
      eCollection 2014 May 6.