scholarly journals New Insights into Xenotransplantation for Cartilage Repair: Porcine Multi-Genetically Modified Chondrocytes as A Promising Cell Source

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2152
Author(s):  
Hanna Tritschler ◽  
Konrad Fischer ◽  
Jochen Seissler ◽  
Jörg Fiedler ◽  
Rebecca Halbgebauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complement Activation ◽  
Genetically Modified ◽  
Gene Expression Level ◽  
Expression Level ◽  
Cartilage Defects ◽  
Specific Cell ◽  
Human Articular Cartilage ◽  
Xenograft Rejection ◽  
Functional Assays

Transplantation of xenogenic porcine chondrocytes could represent a future strategy for the treatment of human articular cartilage defects. Major obstacles are humoral and cellular rejection processes triggered by xenogenic epitopes like α-1,3-Gal and Neu5Gc. Besides knockout (KO) of genes responsible for the biosynthesis of respective epitopes (GGTA1 and CMAH), transgenic expression of human complement inhibitors and anti-apoptotic as well as anti-inflammatory factors (CD46, CD55, CD59, TNFAIP3 and HMOX1) could synergistically prevent hyperacute xenograft rejection. Therefore, chondrocytes from different strains of single- or multi-genetically modified pigs were characterized concerning their protection from xenogeneic complement activation. Articular chondrocytes were isolated from the knee joints of WT, GalTKO, GalT/CMAH-KO, human CD59/CD55//CD46/TNFAIP3/HMOX1-transgenic (TG), GalTKO/TG and GalT/CMAHKO/TG pigs. The tissue-specific effectiveness of the genetic modifications was tested on gene, protein and epitope expression level or by functional assays. After exposure to 20% and 40% normal human serum (NHS), deposition of C3b/iC3b/C3c and formation of the terminal complement complex (TCC, C5b-9) was quantified by specific cell ELISAs, and generation of the anaphylatoxin C5a by ELISA. Chondrocyte lysis was analyzed by Trypan Blue Exclusion Assay. In all respective KO variants, the absence of α -1,3-Gal and Neu5Gc epitope was verified by FACS analysis. In chondrocytes derived from TG animals, expression of CD55 and CD59 could be confirmed on gene and protein level, TNFAIP3 on gene expression level as well as by functional assays and CD46 only on gene expression level whereas transgenic HMOX1 expression was not evident. Complement activation in the presence of NHS indicated mainly effective although incomplete protection against C3b/iC3b/C3c deposition, C5a-generation and C5b-9 formation being lowest in single GalTKO. Chondrocyte viability under exposure to NHS was significantly improved even by single GalTKO and completely preserved by all other variants including TG chondrocytes without KO of xenoepitopes.

The investigation of CD36 scavenger receptor and MSR1 scavenger receptor gene expression level in patients with atherosclerosis

2010 ◽  
Vol 27 ◽  
pp. S66
Author(s):  
M. Piechota ◽  
A. Banaszewska ◽  
E. Guzniczak ◽  
G. Rosinski ◽  
T. Siminiak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Scavenger Receptor ◽  
Gene Expression Level ◽  
Expression Level ◽  
Receptor Gene Expression

The impact of gene-body H3K36me3 patterns on gene expression level changes in chronic myelogenous leukemia

Gene ◽  
2021 ◽  
pp. 145862
Author(s):  
Lu-Qiang Zhang ◽  
Jun-Jie Liu ◽  
Li Liu ◽  
Guo-Liang Fan ◽  
Yan-Nan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Gene Expression Level ◽  
Expression Level ◽  
Gene Body ◽  
The Impact

scholarly journals Elevated Lipocalin-2 Can Indicate the Vascular Inflammation in Patients with Ischemic Stroke

2019 ◽  
Author(s):  
Rajnics P ◽  
◽  
Kellner A ◽  
Nagy F ◽  
Alföldi V ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ischemic Stroke ◽  
Gene Expression Level ◽  
Expression Level ◽  
Neutrophil Granulocytes ◽  
Lipocalin 2 ◽  
Relative Gene Expression ◽  
Thrombotic Risk ◽  
Relative Gene ◽  
Relative Gene Expression Level

Purpose: Elevated level of Lipocalin-2 (LCN2), a new acute phase adipokine, was described after ischemic stroke. A number of researchers feel as though that LCN2 originated from the infiltrating neutrophils and other cells in brain after stroke. Others measured elevated LCN2 expression in arteriosclerotic plaque. Therefore we have investigated LCN2 relative gene expression level of blood neutrophil granulocytes in patients with ischemic stroke to assess if elevated LCN2 is the cause or consequence of ischemic stroke. Methods: Laboratory and anamnestic data were collected, which could have a role in development of thrombo-embolic events in patients with ischemic stroke. RNA based method was used to evaluate the relative gene expression level of LCN2. We calculated Odds Ratio (OR) and Confidence Interval (CI) for the association between LCN2 and ischemic stroke. Results: 34 samples were available for evaluation. The LCN 2 relative gene expression level was decreased in 12 cases. In this group, 91% of patients have Atrial Fibrillation (AF) at the time of hospitalisation. The mean LCN2 relative gene expression value was 64.25% (ranges: 34%-115%) in patients with AF. It was significantly lower than in patients with normal sinus rhythm (409.2%; ranges: 127%-1127%; p=0.0003). The elevated LCN2 relative gene expression level significantly (p=0.012) increases the risk of stroke (OR: 12.6) independently from other factors. Conclusions: High LCN2 expression level seems to have strong positive predictive value on ischemic stroke, and may be useful in thrombotic risk stratification of plaque vulnerability in these patients.

Sequence determinants of prokaryotic gene expression level under heat stress

Gene ◽  
2014 ◽  
Vol 551 (1) ◽  
pp. 92-102 ◽  
Author(s):  
Heng Xiong ◽  
Yi Yang ◽  
Xiao-Pan Hu ◽  
Yi-Ming He ◽  
Bin-Guang Ma
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Gene Expression Level ◽  
Expression Level
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