scholarly journals Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair

2021 ◽  
Vol 22 (2) ◽  
pp. 781
Author(s):  
Inés Maldonado-Lasunción ◽  
Nick O’Neill ◽  
Oliver Umland ◽  
Joost Verhaagen ◽  
Martin Oudega
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Vascular Endothelial ◽  
Glial Derived Neurotrophic Factor ◽  
Transcriptomic Changes ◽  
Endothelial Growth Factor ◽  
Cellular Components ◽  
Hepatocyte Growth ◽  
Go Terms

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.

scholarly journals Novel human Ab against vascular endothelial growth factor receptor 2 shows therapeutic potential for leukemia and prostate cancer

2019 ◽  
Vol 110 (12) ◽  
pp. 3773-3787 ◽  
Author(s):  
Ruei‐Min Lu ◽  
Chiung‐Yi Chiu ◽  
I‐Ju Liu ◽  
Yu‐Ling Chang ◽  
Yaw‐Jen Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Therapeutic Potential ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Angiogenesis-Related Cytokines, RANKL, and Osteoprotegerin in Multiple Myeloma Patients in relation to Clinical Features and Response to Treatment

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
K. Sfiridaki ◽  
C. A. Pappa ◽  
G. Tsirakis ◽  
P. Kanellou ◽  
M. Kaparou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Serum Levels ◽  
Response To Treatment ◽  
Disease Stage ◽  
Vascular Endothelial ◽  
Newly Diagnosed ◽  
Plateau Phase ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

An essential cytokine system for the osteoclast biology in multiple myeloma (MM) consists of the receptor of activator of NF-κB ligand (RANKL), its receptor (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG, soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP, interleukin-6 (IL-6),β2-microglobulin (B2M)], and angiogenic factors [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in 54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above values were higher in MM patients compared to controls and decreased in plateau phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal grade. Significant correlations were found among RANKL and RANKL/OPG with HGF, LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis.

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