A novel bioscaffold with naturally-occurring extracellular matrix promotes hepatocyte survival and vessel patency in mouse models of heterologous transplantation

Biomaterials ◽  
2018 ◽  
Vol 177 ◽  
pp. 52-66 ◽  
Author(s):  
Wei Yang ◽  
Quanyu Chen ◽  
Renpei Xia ◽  
Yujun Zhang ◽  
Ling Shuai ◽  
...  
Author(s):  
Stephanie A. Pumphrey ◽  
Emily Zitek-Morrison ◽  
Stefano Pizzirani ◽  
Dawn M. Meola

Abstract OBJECTIVE To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG). SAMPLE Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs. PROCEDURES A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared. RESULTS Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes. CLINICAL RELEVANCE MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.


2015 ◽  
Vol 29 (3) ◽  
pp. 247-253
Author(s):  
A. Oslobanu ◽  
St.I. Florian

Abstract A biomarker is “a naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified” and it could be used a measurable indicator for the presence or severity of disease state. YKL-40 is a secreted glycoprotein associated with extracellular matrix, a member of the mammalian chitinase-like proteins that is expressed in a several types of solid tumors. Although the implication of this biomarker in tissue remodeling processes or the role in cancer cell proliferation, invasiveness, angiogenesis, and remodeling of the extracellular matrix is going to be well recognized, the regulation and role in glioblastoma multiforme (GBM) progression remains unknown. Using the serum level of YKL-40 as a single screening test in cancer cannot be used, but in association with other tumoral biomarkers and imaging techniques can be a useful tool as a “prognosticator.” Moreover, elucidation of the YKL-40 functions could be an attractive target for antitumor therapy.


2017 ◽  
Vol 131 (12) ◽  
pp. 1283-1285 ◽  
Author(s):  
Mamoru Satoh ◽  
Takahito Nasu ◽  
Takuya Osaki ◽  
Sho Hitomi

In this issue of Clinical Science, Krishna and colleagues describe recent work on thrombospondin-1 (TSP-1) maturation and its association with slower growth of aortic aneurysm in TSP-1 knockdown mouse models. The authors conclude that TSP-1 deficiency promotes maladaptive remodeling of the extracellular matrix (ECM) leading to accelerated aortic aneurysm progression. We comment on a causal relation between TSP-1 and the progression of aortic aneurysm.


Author(s):  
Hyunseung Sun ◽  
Eunmi Kim ◽  
Jihye Ryu ◽  
Hyejin Lee ◽  
Eun-Ae Shin ◽  
...  

AbstractAberrant extracellular matrix and immune cell alterations within the tumor microenvironment promote the pathological progression of liver carcinogenesis. Although transmembrane 4 L six family member 5 (TM4SF5) is involved in liver fibrosis and cancer, its mechanism avoiding immune surveillance during carcinogenesis remains unknown. We investigated how TM4SF5-mediated signaling caused immune evasion using in vitro primary cells and in vivo liver tissues from genetic or chemically induced mouse models. TM4SF5-transgenic and diethylnitrosamine (DEN)-induced liver cancer mouse models exhibited fibrotic and cancerous livers, respectively, with enhanced TM4SF5, pY705STAT3, collagen I, and laminin γ2 levels. These TM4SF5-mediated effects were abolished by TM4SF5 inhibitor, 4′-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC). TM4SF5-dependent tumorigenesis involved natural killer (NK) cell exhaustion-like phenotypes including the reduction of NK cell number or function, which were blocked with TSAHC treatment. TM4SF5 expression in cancer cells downregulated stimulatory ligands and receptors for NK cell cytotoxicity, including SLAMF6, SLAMF7, MICA/B, and others. TM4SF5 suppression or inhibition reduced STAT3 signaling activity and recovered the receptor levels and NK cell surveillance, leading to reduced fibrotic and cancerous phenotypes, and longer survival. Altogether, these findings suggest that TM4SF5-mediated STAT3 activity for extracellular matrix modulation is involved in the progression of liver disease to HCC and that TM4SF5 appears to suppress NK cells during liver carcinogenesis.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Silvia Arpicco ◽  
Giuseppe De Rosa ◽  
Elias Fattal

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.


PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223244 ◽  
Author(s):  
Mallory Morel ◽  
Angela Ruscitto ◽  
Serhiy Pylawka ◽  
Gwendolyn Reeve ◽  
Mildred C. Embree

2017 ◽  
Vol 95 (2) ◽  
pp. 304-309 ◽  
Author(s):  
Pradip K. Biswas ◽  
Edward J. Behrman ◽  
Venkat Gopalan

Salmonella can utilize fructose-asparagine (F-Asn), a naturally occurring Amadori product, as its sole carbon and nitrogen source. Conversion of F-Asn to the common intermediates glucose-6-phosphate, aspartate, and ammonia was predicted to involve the sequential action of an asparaginase, a kinase, and a deglycase. Mutants lacking the deglycase are highly attenuated in mouse models of intestinal inflammation owing to the toxic build-up of the deglycase substrate. The limited distribution of this metabolic pathway in the animal gut microbiome raises the prospects for antibacterial discovery. We report the biochemical characterization of the kinase that was expected to transform fructose-aspartate to 6-phosphofructose-aspartate during F-Asn utilization. In addition to confirming its anticipated function, we determined through studies of fructose-aspartate analogues that this kinase exhibits a substrate-specificity with greater tolerance to changes to the amino acid (including the d-isomer of aspartate) than to the sugar.


2002 ◽  
Vol 115 (14) ◽  
pp. 2817-2828 ◽  
Author(s):  
Cay M. Kielty ◽  
Michael J. Sherratt ◽  
C. Adrian Shuttleworth

Elastic fibres are essential extracellular matrix macromolecules comprising an elastin core surrounded by a mantle of fibrillin-rich microfibrils. They endow connective tissues such as blood vessels, lungs and skin with the critical properties of elasticity and resilience. The biology of elastic fibres is complex because they have multiple components, a tightly regulated developmental deposition, a multi-step hierarchical assembly and unique biomechanical functions. However, their molecular complexity is at last being unravelled by progress in identifying interactions between component molecules, ultrastructural analyses and studies of informative mouse models.


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