Direct Cell–Cell Contact with Chondrocytes Is a Key Mechanism in Multipotent Mesenchymal Stromal Cell-Mediated Chondrogenesis

2015 ◽  
Vol 21 (19-20) ◽  
pp. 2536-2547 ◽  
Author(s):  
Tommy S. de Windt ◽  
Daniel B.F. Saris ◽  
Ineke C.M. Slaper-Cortenbach ◽  
Mattie H.P. van Rijen ◽  
Debby Gawlitta ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Cell Contact ◽  
Multipotent Mesenchymal Stromal Cell ◽  
Direct Cell ◽  
Cell Cell

Abstract 15392: Inflammation and Ischemic Heart Failure: Monocyte-Mediated Cardiac Fibroblast Activation and Matrix Remodeling Through a Direct Cell-Cell Contact Mechanism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Holly E Mewhort ◽  
Brodie D Lipon ◽  
Daniyil A Svystonyuk ◽  
David G Guzzardi ◽  
Paul W Fedak
Keyword(s):  
Peripheral Blood ◽  
Cardiac Fibroblast ◽  
Cell Contact ◽  
Β1 Integrin ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Fibroblast Activation ◽  
Direct Cell ◽  
Tgf Β1 ◽  
Cell Cell

BACKGROUND: Following myocardial infarction (MI), activated cardiac myofibroblasts facilitate extracellular matrix (ECM) remodeling to prevent mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. In this study, we explored the effects of peripheral blood monocytes on human cardiac fibroblast activation in a 3D ECM microenvironment. METHODS/RESULTS: Human cardiac fibroblasts isolated from surgical human heart biopsies were seeded into 3D collagen matrices. Peripheral blood monocytes isolated from healthy human donors were co-cultured with fibroblasts. Monocytes increased fibroblast activation measured by collagen ECM contraction (17.9±11.1% increase; p<0.01) and resulted in local ECM remodeling observed by confocal microscopy. Under co-culture conditions that prevent cell-cell contact but allow interaction via paracrine factors, monocytes had minimal effects on fibroblast activation (6.4±7.0 vs.17.9±11.1% increase, respectively; p<0.01). Multiplex analysis of the co-culture media revealed an increase in the paracrine factors Transforming Growth Factor-beta 1 (TGF-β1) and Matrix Metalloproteinase 9 when monocytes and fibroblasts were cultured under cell-cell contact conditions (162.2±11.7pg/mL and 17.5±0.5ng/mL, respectively, vs. 21.8±5.7pg/mL and 4.9 ±0.4ng/mL; p<0.001). TGF-β1 blockade abolished monocyte induced cardiac fibroblast activation, as did β1-integrin. These data suggest direct cell-cell interaction between monocytes and cardiac fibroblasts through β1-integrin results in TGF-β1 release facilitating fibroblast activation and matrix remodeling. CONCLUSION: For the first time, we demonstrate that peripheral blood monocytes stimulate human cardiac fibroblast activation through a mechanism involving TGF-β1 release as a consequence of direct cell-cell interaction through β1-integrin. These data implicate inflammation as a driver of cardiac fibrosis post-MI, highlighting potential novel therapeutic targets for the treatment of ischemic HF.

scholarly journals Combination of the multipotent mesenchymal stromal cell transplantation with administration of temozolomide increases survival of rats with experimental glioblastoma

2015 ◽  
Vol 12 (2) ◽  
pp. 2828-2834 ◽  
Author(s):  
IGOR BRYUKHOVETSKIY ◽  
ANDREI BRYUKHOVETSKY ◽  
YURI KHOTIMCHENKO ◽  
POLINA MISCHENKO ◽  
ELENA TOLOK ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Multipotent Mesenchymal Stromal Cell

scholarly journals Hypoxia-Controlled EphA3 Marks a Human Endometrium-Derived Multipotent Mesenchymal Stromal Cell that Supports Vascular Growth

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112106 ◽  
Author(s):  
Catherine To ◽  
Rae H. Farnsworth ◽  
Mary E. Vail ◽  
Chanly Chheang ◽  
Caroline E. Gargett ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Human Endometrium ◽  
Multipotent Mesenchymal Stromal Cell ◽  
Vascular Growth
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