scholarly journals Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

2014 ◽  
Vol 5 ◽  
Author(s):  
Nicoline W. Smit ◽  
Ruben Coronel
2014 ◽  
Vol 127 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
A. E. Zemljic-Harpf ◽  
J. C. Godoy ◽  
O. Platoshyn ◽  
E. K. Asfaw ◽  
A. R. Busija ◽  
...  

Stem Cells ◽  
2006 ◽  
Vol 24 (7) ◽  
pp. 1654-1667 ◽  
Author(s):  
James E. Huettner ◽  
Aiwu Lu ◽  
Yun Qu ◽  
Yingji Wu ◽  
Mijeong Kim ◽  
...  

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 498-505 ◽  
Author(s):  
Jose A. Cancelas ◽  
Wendy L. M. Koevoet ◽  
Alexandra E. de Koning ◽  
Angelique E. M. Mayen ◽  
Elwin J. C. Rombouts ◽  
...  

Abstract Gap junctions (GJs) provide for a unique system of intercellular communication (IC) allowing rapid transport of small molecules from cell to cell. GJs are formed by a large family of proteins named connexins (Cxs). Cx43 has been considered as the predominantly expressed Cx by hematopoietic-supporting stroma. To investigate the role of the Cx family in hemopoiesis, we analyzed the expression of 11 different Cx species in different stromal cell lines derived from murine bone marrow (BM) or fetal liver (FL). We found that up to 5 Cxs are expressed in FL stromal cells (Cx43, Cx45, Cx30.3, Cx31, and Cx31.1), whereas only Cx43, Cx45, and Cx31 were clearly detectable in BM stromal cells. In vivo, the Cx43-deficient 14.5- to 15-day FL cobblestone area–forming cells (CAFC)-week 1-4 and colony-forming unit contents were 26%-38% and 39%-47% lower than in their wild-type counterparts, respectively. The reintroduction of the Cx43 gene into Cx43-deficient FL stromal cells was able to restore their diminished IC to the level of the wild-type FL stromal cells. In addition, these Cx43-reintroduced stromal cells showed an increased support ability (3.7-fold) for CAFC-week 1 in normal mouse BM and 5-fold higher supportive ability for CAFC-week 4 in 5-fluorouracil-treated BM cells as compared with Cx43-deficient FL stromal cells. These findings suggest that stromal Cx43-mediated IC, although not responsible for all GJ-mediated IC of stromal cells, plays a role in the supportive ability for hemopoietic progenitors and stem cells.


2016 ◽  
Vol 146 (5) ◽  
pp. 529-537 ◽  
Author(s):  
Anja Beckmann ◽  
Madline Schubert ◽  
Nadine Hainz ◽  
Alexandra Haase ◽  
Ulrich Martin ◽  
...  

2017 ◽  
Vol 121 (6) ◽  
Author(s):  
Atsushi Tachibana ◽  
Michelle R. Santoso ◽  
Morteza Mahmoudi ◽  
Praveen Shukla ◽  
Lei Wang ◽  
...  

Rationale: Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. Objective: To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. Methods and Results: Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. Conclusions: This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.


2013 ◽  
Vol 17 (6) ◽  
pp. 774-781 ◽  
Author(s):  
Jennifer Petsche Connell ◽  
Emily Augustini ◽  
Kenneth J. Moise ◽  
Anthony Johnson ◽  
Jeffrey G. Jacot

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