scholarly journals Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation

2019 ◽  
Vol 11 (485) ◽  
pp. eaau6934 ◽  
Author(s):  
Robert D. Kirkton ◽  
Maribel Santiago-Maysonet ◽  
Jeffrey H. Lawson ◽  
William E. Tente ◽  
Shannon L. M. Dahl ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Progenitor Cell ◽  
Smooth Muscle Actin ◽  
Small Samples ◽  
Mechanical Degradation ◽  
Matrix Remodeling ◽  
Self Healing ◽  
Alpha Smooth Muscle Actin ◽  
Surgical Interventions ◽  
Host Cell Response

Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease. In rare cases, small samples of HAV were recovered during routine surgical interventions and used to examine the temporal and spatial pattern of the host cell response to the HAV after implantation, from 16 to 200 weeks. We observed a substantial influx of alpha smooth muscle actin (αSMA)–expressing cells into the HAV that progressively matured and circumferentially aligned in the HAV wall. These cells were supported by microvasculature initially formed by CD34+/CD31+ cells in the neoadventitia and later maintained by CD34−/CD31+ endothelial cells in the media and lumen of the HAV. Nestin+ progenitor cells differentiated into either αSMA+ or CD31+ cells and may contribute to early recellularization and self-repair of the HAV. A mesenchymal stem cell–like CD90+ progenitor cell population increased in number with duration of implantation. Our results suggest that host myogenic, endothelial, and progenitor cell repopulation of HAVs transforms these previously acellular vessels into functional multilayered living tissues that maintain blood transport and exhibit self-healing after cannulation injury, effectively rendering these vessels like the patient’s own blood vessel.

A Pyruvate-Buffered Dialysis Fluid Induces Less Peritoneal Angiogenesis and Fibrosis than a Conventional Solution

2008 ◽  
Vol 28 (5) ◽  
pp. 487-496 ◽  
Author(s):  
Roos van Westrhenen ◽  
Machteld M. Zweers ◽  
Cindy Kunne ◽  
Dirk R. de Waart ◽  
Allard C. van der Wal ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Degradation Products ◽  
Smooth Muscle Actin ◽  
Total Surface Area ◽  
Exposure Model ◽  
Peritoneal Membrane ◽  
Negative Effects ◽  
Alpha Smooth Muscle Actin ◽  
Peritoneal Tissue ◽  
Conventional Solution

Background Conventional lactate-buffered peritoneal dialysis (PD) fluids containing glucose and glucose degradation products are believed to contribute to the development of fibrosis and angiogenesis in the dialyzed peritoneum. To reduce potential negative effects of lactate, pyruvate was substituted as a buffer and its effects on peritoneal pathological alterations were studied in a chronic peritoneal exposure model in the rat. Methods 20 Wistar rats were infused intraperitoneally with pyruvate-buffered ( n = 9) or lactate-buffered PD fluid. After 20 weeks of daily infusion, peritoneal function was assessed. In omental peritoneal tissue, the number of blood vessels was analyzed following alpha-smooth muscle actin staining. The degree of fibrosis was quantitated in Picro Sirius Red-stained sections and by assessment of the hydroxyproline content. Plasma lactate/pyruvate and beta-hydroxybutyrate/acetoacetate (BBA/AA) ratios were determined. Plasma and dialysate vascular endothelial growth factor (VEGF) levels were quantitated by ELISA. Results The mass transfer area coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium was lower in pyruvate-treated animals compared to the lactatetreated group (0.11 vs 0.05 mL/min, p < 0.05, and 78% vs 89%, p < 0.05). The BBA/AA ratio tended to be lower in the pyruvate animals ( p = 0.07). The number of blood vessels was lower in pyruvate-treated animals (16 vs 37 per field, p < 0.001). Total surface area, luminal area, and wall/total area of the vessels were larger in the pyruvate group. The degree of fibrosis was lower in intersegmental and perivascular areas of pyruvate-exposed animals. Effluent VEGF was higher in the pyruvate group. Conclusions Replacement of lactate by pyruvate resulted in changes in peritoneal solute transport, accompanied by a reduction in both peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel mechanisms to reduce glucose-driven alterations to the peritoneal membrane in PD patients.

scholarly journals Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study

2018 ◽  
Vol 21 (2) ◽  
pp. 165-172
Author(s):  
Chiara Valtolina ◽  
Joris H Robben ◽  
Robert P Favier ◽  
Jan Rothuizen ◽  
Guy CM Grinwis ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Morphological Study ◽  
Progenitor Cell ◽  
Smooth Muscle Actin ◽  
Spatial Association ◽  
Cell Types ◽  
Hepatic Progenitor Cell ◽  
Hepatic Lipidosis ◽  
Alpha Smooth Muscle Actin ◽  
Cell Niche

Objectives The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). Methods Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. Results HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. Conclusions and relevance This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

Anisotropic Strain Fields Enhance Matrix Remodeling Through Elevated TGF-β Signaling

2011 ◽  
Author(s):  
Russell Gould ◽  
Karen Chin ◽  
Puifai Santisakultam ◽  
Amanda Dropkin ◽  
Jennifer Richards ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Smooth Muscle Actin ◽  
Matrix Remodeling ◽  
Alpha Smooth Muscle Actin ◽  
Anisotropic Strain ◽  
Unique Effect ◽  
Engineered Tissue ◽  
Growth Factor Beta

In this work, we demonstrate the unique effect of controlled anisotropic strain on fibroblast behavior in 3D engineered tissue environments. Anisotropy of biaxial strain resulted in increased cellular orientation and collagen fiber alignment. Transforming growth factor beta-1 (TGFβ1) gene expression and pSmad2 nuclear translocation increased with biaxial directionality. Myofibroblastic alpha-smooth muscle actin (α-SMA) decreased with applied strain similar to mechanically unloaded hydrogels. Collectively, these results demonstrate a novel mechanobiological mechanism by which fibroblasts develop rapid anisotropic matrix striation while maintaining phenotype quiescence.

scholarly journals Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

2021 ◽  
Vol 22 (21) ◽  
pp. 11911
Author(s):  
Jiranuwat Sapudom ◽  
Mei ElGindi ◽  
Marc Arnoux ◽  
Nizar Drou ◽  
Anna Garcia-Sabaté ◽  
...  
Keyword(s):  
Simulated Microgravity ◽  
Smooth Muscle Actin ◽  
Healing Process ◽  
3D Culture ◽  
3D Cell Culture ◽  
Wound Healing Process ◽  
Interstitial Tissue ◽  
Matrix Remodeling ◽  
Alpha Smooth Muscle Actin ◽  
Matrix Production

Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1g control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions.

Oncocytic Lipoadenoma: Report of 3 Rare Cases Involving the Parotid Gland, Including a Synchronous Presentation With Paraganglioma of the Right Carotid Bifurcation and Literature Review

2021 ◽  
pp. 106689692110219
Author(s):  
John L.S. Cunha ◽  
Marco A. Peñalonzo ◽  
Ciro D. Soares ◽  
Bruno A.B. de Andrade ◽  
Mário J. Romañach ◽  
...  
Keyword(s):  
English Language ◽  
Smooth Muscle Actin ◽  
Salivary Gland Tumor ◽  
Surgical Excision ◽  
Carotid Bifurcation ◽  
Alpha Smooth Muscle Actin ◽  
S 100 ◽  
The Right ◽  
Adequate Management ◽  
Adipose Cells

Oncocytic lipoadenoma (OL) is a rare salivary gland tumor characterized by the presence of oncocytic cells and mature adipose tissue. To date, only 30 cases of OL have been reported in the English-language literature. We present 3 additional OL cases involving the parotid, including a synchronous presentation with paraganglioma of the right carotid bifurcation. Microscopically, both the OLs were composed of a mixed population of oncocytes and adipocytes in varying proportions surrounded by a thin, connective tissue fibrous capsule. Oncocytes were positive for pan-cytokeratins (CKs) AE1/AE3, epithelial membrane antigen, CK5, CK7, CK14, CK18, and CK19. Calponin, p63, alpha-smooth muscle actin, and carcinoembryonic antigen were negative. Vimentin and S-100 protein were positive only in adipose cells. Despite distinctive morphologic features, OL is often misdiagnosed, given its rarity. We hope to contribute to surgeons’ and pathologists’ awareness and knowledge regarding the existence of this tumor and provide adequate management through conservative surgical excision.

scholarly journals The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1861
Author(s):  
Jemima Seidenberg ◽  
Mara Stellato ◽  
Amela Hukara ◽  
Burkhard Ludewig ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Beclin 1 ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Background: Pathological activation of cardiac fibroblasts is a key step in development and progression of cardiac fibrosis and heart failure. This process has been associated with enhanced autophagocytosis, but molecular mechanisms remain largely unknown. Methods and Results: Immunohistochemical analysis of endomyocardial biopsies showed increased activation of autophagy in fibrotic hearts of patients with inflammatory cardiomyopathy. In vitro experiments using mouse and human cardiac fibroblasts confirmed that blockade of autophagy with Bafilomycin A1 inhibited fibroblast-to-myofibroblast transition induced by transforming growth factor (TGF)-β. Next, we observed that cardiac fibroblasts obtained from mice overexpressing transcription factor Fos-related antigen 2 (Fosl-2tg) expressed elevated protein levels of autophagy markers: the lipid modified form of microtubule-associated protein 1A/1B-light chain 3B (LC3BII), Beclin-1 and autophagy related 5 (Atg5). In complementary experiments, silencing of Fosl-2 with antisense GapmeR oligonucleotides suppressed production of type I collagen, myofibroblast marker alpha smooth muscle actin and autophagy marker Beclin-1 in cardiac fibroblasts. On the other hand, silencing of either LC3B or Beclin-1 reduced Fosl-2 levels in TGF-β-activated, but not in unstimulated cells. Using a cardiac hypertrophy model induced by continuous infusion of angiotensin II with osmotic minipumps, we confirmed that mice lacking either Fosl-2 (Ccl19CreFosl2flox/flox) or Atg5 (Ccl19CreAtg5flox/flox) in stromal cells were protected from cardiac fibrosis. Conclusion: Our findings demonstrate that Fosl-2 regulates autophagocytosis and the TGF-β-Fosl-2-autophagy axis controls differentiation of cardiac fibroblasts. These data provide a new insight for the development of pharmaceutical targets in cardiac fibrosis.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

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