scholarly journals Stromal Cell-Derived Factor-1 Enhances the Therapeutic Effects of Human Endometrial Regenerative Cells in a Mouse Sepsis Model

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Wang Jin ◽  
Yiming Zhao ◽  
Yonghao Hu ◽  
Dingding Yu ◽  
Xiang Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Tissue Damage ◽  
Stromal Cell ◽  
Therapeutic Effects ◽  
Sepsis Model ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells ◽  
Stromal Cell Derived Factor ◽  
Mouse Sepsis Model

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells obtained from human menstrual blood, whose positive therapeutic effects have been validated in several experimental models. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, plays an important role in the migration of mesenchymal stromal cells. The purpose of this study was to investigate the role of the SDF-1/CXCR4 pathway in the therapeutic effects of ERCs in a mouse sepsis model. Through preexperiment and confirmation, wild-type C57BL/6 mice were intraperitoneally injected with 10 mg/kg lipopolysaccharide (LPS). The therapeutic effects of ERCs with different pretreatments were evaluated by assessing sepsis-related symptoms, detecting tissue damage and measuring levels of inflammatory and oxidative stress-related factors. The in vitro experiments demonstrated that there was a much higher CXCR4 expression on ERCs when they were cocultured with SDF-1. The ex vivo experiment results showed that SDF-1 expression significantly increased in mouse tissues. Further experiments also confirmed that, compared with the unmodified ERC treatment group, SDF-1 pretreatment significantly enhanced the therapeutic effects of ERCs on alleviating sepsis symptoms, ameliorating pathological changes, reducing Bax level, and increasing Bcl-2 and PCNA expressions in mouse liver tissues. Furthermore, it was also found that SDF-1-pretreated ERCs contributed to reducing the levels of proinflammatory cytokines (TNF-α, IL-1β) and increasing the levels of anti-inflammatory factors (IL-4, IL10) in mouse serum, liver, and lung. Moreover, SDF-1-pretreated ERCs could also significantly decrease the levels of iNOS and MDA and increase the expression of Nrf2, HO-1, and SOD in liver tissues. Taken together, these results indicate that SDF-1 pretreatment plays a key role in improving the therapeutic effects of ERCs in alleviating sepsis-related symptoms, reducing tissue damage, regulating inflammatory imbalance, and relieving oxidative stress in a mouse sepsis model, which provides more possibilities for the clinical application of ERCs in sepsis and relevant diseases.

scholarly journals Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

2020 ◽  
Author(s):  
Dingding Yu ◽  
Yiming Zhao ◽  
Yonghao Hu ◽  
Dejun Kong ◽  
Wang Jin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tap Water ◽  
Body Weight Loss ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Endometrial Regenerative Cells ◽  
Tnf Α ◽  
Regenerative Cells ◽  
Dickkopf 1

Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1low-ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1low-ERCs) and glucocorticoid-treated ERCs (DKK1high-ERCs) were injected (1 million/mouse/day, i.v.) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1low-ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2, CD4+CD25+FOXP3+Treg, and CD68+CD206+macrophages in spleens were also significantly upregulated in DKK1low-ERC group (p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1low-ERC group (p < 0.01 vs. other groups). Conclusions DKK1low-ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

scholarly journals Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

2020 ◽  
Author(s):  
Dingding Yu ◽  
Yiming Zhao ◽  
Yonghao Hu ◽  
Dejun Kong ◽  
Wang Jin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tap Water ◽  
Body Weight Loss ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Endometrial Regenerative Cells ◽  
Tnf Α ◽  
Regenerative Cells ◽  
Dickkopf 1

Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1 low -ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1 low -ERCs) and glucocorticoid-treated ERCs (DKK1 high -ERCs) were injected (1 million/mouse/day, i.v. ) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1 low -ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4 + IL-4 + Th2, CD4 + CD25 + FOXP3 + Treg, and CD68 + CD206 + macrophages in spleens were also significantly upregulated in DKK1 low -ERC group ( p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1 low -ERC group ( p < 0.01 vs. other groups). Conclusions DKK1 low -ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

scholarly journals Expression of Stromal Cell–Derived Factor-1 by Mesenchymal Stromal Cells Impacts Neutrophil Function During Sepsis

2020 ◽  
Vol 48 (5) ◽  
pp. e409-e417
Author(s):  
Min-Young Kwon ◽  
Sailaja Ghanta ◽  
Julie Ng ◽  
Konstantin Tsoyi ◽  
James A. Lederer ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Neutrophil Function ◽  
Stromal Cell Derived Factor

scholarly journals New Mechanical Fat Separation Technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST)

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
H Eray Copcu ◽  
Sule Oztan
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Retention Rate ◽  
High Rate ◽  
Cell Transfer ◽  
Fat Tissue ◽  
Cell Counts ◽  
Tissue Transfer ◽  
Regenerative Cells

Abstract Background Adipose tissue is not only a very important source of filler but also the body’s greatest source of regenerative cells. Objectives In this study, adipose tissue was cut to the desired dimensions using ultra-sharp blade systems to avoid excessive blunt pressure and applied to various anatomical areas—a procedure known as adjustable regenerative adipose-tissue transfer (ARAT). Mechanical stromal cell transfer (MEST) of regenerative cells from fat tissue was also examined. Methods ARAT, MEST, or a combination of these was applied in the facial area of a total of 24 patients who were followed for at least 24 months. The integrity of the fat tissue cut with different diameter blades is shown histopathologically. The number and viability of the stromal cells obtained were evaluated and secretome analyses were performed. Patient and surgeon satisfaction were assessed with a visual analog scale. Results With the ARAT technique, the desired size fat grafts were obtained between 4000- and 200-micron diameters and applied at varying depths to different aesthetic units of the face, and a guide was developed. In MEST, stromal cells were obtained from 100 mL of condensed fat using different indication-based protocols with 93% mean viability and cell counts of 28.66 to 88.88 × 106. Conclusions There are 2 main complications in fat grafting: visibility in thin skin and a low retention rate. The ARAT technique can be used to prevent these 2 complications. MEST, on the other hand, obtains a high rate of fat and viable stromal cells without applying excessive blunt pressure. Level of Evidence: 4

Vergleich des Regenerativen Zytokinprofils von Adipose Derived Stromal Cells (ASCs) Gewonnen Mittels Abdominoplastik, Suction Assisted Liposuction (SAL) und Ultrasound Assisted Liposuction (UAL)

2018 ◽  
Vol 50 (02) ◽  
pp. 74-82
Author(s):  
Matthias Michael Aitzetmüller ◽  
Hans-Günther Machens ◽  
Arndt F Schilling ◽  
Dominik Duscher
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Vascular Endothelial ◽  
Adipose Derived Stromal Cells ◽  
Chemotactic Protein ◽  
Ultrasound Assisted ◽  
Stromal Cell Derived Factor ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

Zusammenfassung Einleitung Mesenchymale Stromazellen sind aufgrund ihres regenerativen Potentials schon in zahlreichen Fachgebieten der Medizin im klinischen Einsatz. In der Plastischen Chirurgie stehen vor allem Fettstammzellen (Adipose derived stromal cells = ASCs) aus Lipoasopirat im Mittelpunkt der rezenten Forschung. Die Fähigkeit zur Ausschüttung von regenerativen Zytokinen ist der Schlüsselmechanismus im therapeutischen Einsatz von ASCs. Es sind zurzeit eine Vielzahl an Methoden und Geräten zur Lipoaspiratgewinnung in der klinischen Anwendung. Bei den meisten dieser Geräte sind die Auswirkungen auf die regenerativen Eigenschaften der ASCs noch weitgehend ungeklärt. Ziel dieser Studie ist der Vergleich der Expression von wesentlichen regenerativen Zytokinen von ASCs, gewonnen mittels dreier Standardverfahren der Plastischen Chirurgie: Abdominoplastik, Suction assisted Liposuction (SAL) und Ultrasound assisted Liposuction (UAL). Patienten und Methoden UAL und SAL Lipoaspirate wurden jeweils von 3 gesunden weiblichen Probanden gewonnen, be vor eine Abdominoplastik an denselben Patienten durchgeführt wurde. ASCs wurden aus UAL und SAL Lipoaspiraten sowie aus den Abdominoplastikresektaten isoliert und die RNA-Expression von wichtigen regenerativen Zytokinen (HGF (hepatocyte growth factor), FGF-2 (basic fibroblast growth factor), MCP-1 (monocyte chemotactic protein 1), SDF-1 (stromal cell-derived factor 1) und VEGF (vascular endothelial growth factor) verglichen. Resultate Es zeigte sich kein Unterschied hinsichtlich der Expression von HGF, FGF-2, SDF-1 und VEGF zwischen den einzelnen Proben, jedoch eine signifikant erhöhte Expression von MCP-1 in ASCs gewonnen aus UAL-Lipoaspirat. Conclusio UAL stellt bezüglich Einfluss auf das ASC Expressionsprofil von Schlüsselzytokinen der Gewebserneuerung eine mit SAL zumindest vergleichbare Methode dar. Sowohl UAL als auch SAL Lipoaspirate sind geeignet zur Gewinnung von funktionellen ASCs vergleichbar mit minimal manipulierten Zellen aus Abdominoplastikresektaten.

Stromal Cell-Derived Factor 1α Induces Accumulation of Intraveneously Administered Marrow-Derived Stromal Cells in the Partially Obstructed Rat Bladder

2012 ◽  
Vol 4 (3) ◽  
pp. 154-160
Author(s):  
Hiroshi SANO ◽  
Takahiko MITSUI ◽  
Yukiko KANNO ◽  
Kimihiko MORIYA ◽  
Hiroshi TANAKA ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Stromal Cell ◽  
Rat Bladder ◽  
Stromal Cell Derived Factor
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