scholarly journals Crosstalk of Endothelial and Mesenchymal Stromal Cells under Tissue-Related O2

2021 ◽  
Vol 1 (2) ◽  
pp. 116-136
Author(s):  
Olga Zhidkova ◽  
Elena Andreeva ◽  
Mariia Ezdakova ◽  
Ludmila Buravkova

Mesenchymal stromal cells (MSCs) are considered a valuable tool for cell therapy. After systemic administration, the outcome of MSCs and endothelial cells (ECs) interactions strongly depend on the local microenvironment and tissue O2 levels in particular. In vitro analysis of EC effects on MSC regenerative potential in co-culture was performed after short-term interaction at “physiological” hypoxia (5% O2) and acute hypoxic stress (0.1% O2). At 5% O2, MSCs retained stromal phenotype and CFU-f numbers, osteogenic RUNX2 was upregulated. A shift in the expression of adhesion molecules, and an increase in transcription/synthesis of IL-6, IL-8 contributed to facilitation of directed migration of MSCs. In the presence of MSCs, manifestations of oxidative stress in ECs were attenuated, and a decrease in adhesion of PBMCs to TNF-α-activated ECs was observed. Under 0.1% O2, reciprocal effects of ECs and MSCs were similar to those at 5% O2. Meanwhile, upregulation of RUNX2 was canceled, IL-6 decreased, and IL-8 significantly increased. “Protective” effects of MSCs on TNF-α-ECs were less pronounced, manifested as NOS3 downregulation and intracellular NO elevation. Therefore, interaction with ECs at “physiological” hypoxia enhanced pro-regenerative capacities of MSCs including migration and anti-inflammatory modulation of ECs. Under acute hypoxic stress, the stimulating effects of ECs on MSCs and the “protective” potential of MSCs towards TNF-α-ECs were attenuated.

2014 ◽  
Vol 23 (11) ◽  
pp. 1217-1232 ◽  
Author(s):  
Marta E. Castro-Manrreza ◽  
Hector Mayani ◽  
Alberto Monroy-García ◽  
Eugenia Flores-Figueroa ◽  
Karina Chávez-Rueda ◽  
...  

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190082 ◽  
Author(s):  
Sabrina Sella ◽  
Valentina Adami ◽  
Eliana Amati ◽  
Martina Bernardi ◽  
Katia Chieregato ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Olga O. Udartseva ◽  
Margarita V. Lobanova ◽  
Elena R. Andreeva ◽  
Sergey V. Buravkov ◽  
Irina V. Ogneva ◽  
...  

The ability of mesenchymal stromal (stem) cells (MSCs) to be mobilised from their local depot towards sites of injury and to participate in tissue repair makes these cells promising candidates for cell therapy. Physiological O2tension in an MSC niche in vivo is about 4–7%. However, most in vitro studies of MSC functional activity are performed at 20% O2. Therefore, this study focused on the effects of short-term hypoxic stress (0.1% O2, 24 h) on adipose tissue-derived MSC motility at tissue-related O2level. No significant changes in integrin expression were detected after short-term hypoxic stress. However, O2deprivation provoked vimentin disassembly and actin polymerisation and increased cell stiffness. In addition, hypoxic stress induced the downregulation ofACTR3, DSTN, MACF1, MID1, MYPT1, NCK1, ROCK1, TIAM1, andWASF1expression, the products of which are known to be involved in leading edge formation and cell translocation. These changes were accompanied by the attenuation of targeted and nontargeted migration of MSCs after short-term hypoxic exposure, as demonstrated in scratch and transwell migration assays. These results indicate that acute hypoxic stress can modulate MSC function in their native milieu, preventing their mobilisation from sites of injury.


2015 ◽  
Vol 308 (12) ◽  
pp. F1474-F1483 ◽  
Author(s):  
Jing Zhao ◽  
Yoon Kow Young ◽  
Julie Fradette ◽  
Nicoletta Eliopoulos

The efficacy of cell therapy for many diseases can be limited by the poor survival of implanted cells in an environment of tissue injury. Melatonin has been reported to have antioxidative and antiapoptotic effects. Adipose tissue-derived mesenchymal stromal cells (ASCs), cells easily obtained in high amounts and with minimal discomfort, have shown great promise in cell therapy applications, such as in acute kidney injury. We hypothesized that melatonin pretreatment of human ASCs (hASCs) would improve their renoprotective and prosurvival effects. We therefore investigated the action of melatonin on hASCs, as well as the effect of the resulting hASCs-conditioned media (CM) on human kidney cells exposed to oxidative and apoptotic injury-provoking doses of cisplatin. Our results demonstrated that pretreatment of hASCs with melatonin, 100 μM for 3 h, significantly increased their proliferation and their expression of prosurvival P-Erk1/2 and P-Akt, and of antioxidative enzymes catalase and heme oxygenase (HO)-1. In addition, the CM from hASCs pretreated with melatonin provoked a significantly higher proliferation and migration of HK-2 human kidney epithelial cells. Furthermore, this CM exerted significantly higher prosurvival and antiapoptotic actions on HK-2 cells exposed to cisplatin in vitro. Western blot analysis showed higher expression of P-Erk1/2, Bcl-2, SOD-1, and HO-1 in the HK-2 cells exposed to cisplatin in the presence of CM from melatonin-pretreated hASCs. In sum, our study revealed that in vitro pretreatment of hASCs with melatonin may significantly enhance their survival and their therapeutic effectiveness on injured tissue.


2014 ◽  
Vol 84 (4) ◽  
pp. 680-686 ◽  
Author(s):  
In-Hye Kim ◽  
Hyo-Sang Park ◽  
Young Kyung Kim ◽  
Kyo-Han Kim ◽  
Tae-Yub Kwon

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