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 ◽  
...  

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.

Author(s):  
Francesco Bellanti ◽  
Giuseppe Pannone ◽  
Nicola Tartaglia ◽  
Gaetano Serviddio

2014 ◽  
Vol 201 (3) ◽  
pp. 345-352 ◽  
Author(s):  
H.S. Kruitwagen ◽  
B. Spee ◽  
C.S. Viebahn ◽  
H.B. Venema ◽  
L.C. Penning ◽  
...  

1995 ◽  
Vol 269 (4) ◽  
pp. G532-G541 ◽  
Author(s):  
G. A. Ramm ◽  
R. S. Britton ◽  
R. O'Neill ◽  
W. S. Blaner ◽  
B. R. Bacon

Lipocytes have been classified as vitamin A-storing, desmin-positive cells. In hepatic fibrogenesis, lipocytes transform into myofibroblasts, which express alpha-smooth muscle actin (alpha-SMA) and produce increased amounts of collagen. We isolated a population of vitamin A-poor lipocytes (VAPL) from normal rat liver and examined the morphological and biochemical differences between VAPL and vitamin A-replete lipocytes (VARL). Desmin and alpha-SMA expression were determined by Western blot in quiescent cells and in cells activated by culture on uncoated plastic. Both cell types were alpha-SMA-negative; however, in contrast to VARL, freshly isolated VAPL did not contain desmin. Desmin expression was induced in VAPL on activation. With time in culture, both VAPL and VARL expressed alpha-SMA and produced collagen, indicative of transformation to myofibroblasts. Ferritin receptor expression was demonstrated in cultured VARL after 1 day and in VAPL after 5 days, indicating that this is an early marker of lipocyte activation. After 7 days, VARL and VAPL were indistinguishable in terms of desmin, ferritin receptor expression, and collagen production. This study demonstrates the first isolation and characterization of two distinct quiescent subpopulations of lipocytes from normal rat liver: desmin-negative VAPL and desmin-positive VARL. Both populations of cells can be activated to myofibroblasts, the phenotype associated with hepatic fibrogenesis.


2017 ◽  
Vol 20 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Corma MA Otte ◽  
Chiara Valtolina ◽  
Sandra Vreman ◽  
Siobhan Hubers ◽  
Monique E van Wolferen ◽  
...  

Objectives The aim of the study was to compare the hepatic progenitor cell niche in healthy feline livers and the liver tissue of cats with lymphocytic cholangitis. Methods Immunohistochemical stainings for vimentin, laminin, beta (β)-catenin and Notch1 intracellular domain (NICD) were used on formalin-fixed liver biopsies from affected (n = 12) and unaffected cats (n = 2). Results All immunohistochemical markers used were expressed in more cells, or more intensely, in the liver tissue of cats with lymphocytic cholangitis than in the liver tissue of unaffected cats. Conclusions and relevance Enhanced expression of vimentin, laminin, cytoplasmic/nuclear β-catenin and NICD in liver biopsies from cats with lymphocytic cholangitis indicates that the hepatic progenitor cell (HPC) niche is remodelled and activated. HPCs might provide insights into new regenerative treatment options for lymphocytic cholangitis in cats in the future.


2019 ◽  
Vol 11 (485) ◽  
pp. eaau6934 ◽  
Author(s):  
Robert D. Kirkton ◽  
Maribel Santiago-Maysonet ◽  
Jeffrey H. Lawson ◽  
William E. Tente ◽  
Shannon L. M. Dahl ◽  
...  

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.


1990 ◽  
Vol 38 (11) ◽  
pp. 1541-1547 ◽  
Author(s):  
A Sapino ◽  
L Macrì ◽  
P Gugliotta ◽  
G Bussolati

To study cell proliferation in different cell types and segments of the mammary gland, we devised a dual staining procedure, combining nuclear labeling by 5-bromo-2'-deoxy-uridine (BrdU) uptake (revealed by a dark-brown precipitate) and an alternative (red or blue) cytoplasmic labeling by antibodies specific for the differentiation proteins of epithelial, myoepithelial, and secretory cell types. The following markers, revealed by APAAP or beta-galactosidase procedure, were selected: alpha-smooth muscle actin for the myoepithelial cells, keratin (detected by AE1 monoclonal) for the luminal epithelial cells, alpha-lactalbumin and beta-casein for the secretory cells. To follow the full process of organogenesis, the study was conducted in mouse mammary glands from virgin, primed, and lactating animals and from glands cultured in vitro under specific hormone stimulation. Cell proliferation was localized mainly in focal areas (end buds), and mostly corresponded to "null" undifferentiated cells. Estrogen and progestin stimulation induced a relative increase of proliferating differentiated cells of either epithelial or myoepithelial type, localized in ducts and alveolar structures. Prolactin stimulation induced proliferation in secretory cells.


2016 ◽  
Vol 113 (15) ◽  
pp. E2162-E2171 ◽  
Author(s):  
Lin-ting Hsia ◽  
Neil Ashley ◽  
Djamila Ouaret ◽  
Lai Mun Wang ◽  
Jennifer Wilding ◽  
...  

Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumor progression. Myofibroblasts previously have been distinguished from normal fibroblasts mostly by the expression of α smooth muscle actin (αSMA). We now have identified AOC3 (amine oxidase, copper containing 3), a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast-reacting mAb PR2D3. The normal and tumor tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by nonenzymatic procedures. Whole-genome microarray mRNA-expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly differentially expressed in these two cell types: NKX2-3 and LRRC17 in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. TGFβ substantially down-regulated AOC3 expression in myofibroblasts but in skin fibroblasts it dramatically increased the expression of αSMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and increased expression of the fibroblast-associated gene SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3, and other markers, are a distinctly different cell type from TGFβ-activated fibroblasts.


The Lancet ◽  
2013 ◽  
Vol 381 ◽  
pp. S23 ◽  
Author(s):  
TG Bird ◽  
L Boutler ◽  
A Cole ◽  
S Lorenzini ◽  
WY Lu ◽  
...  

1989 ◽  
Vol 37 (3) ◽  
pp. 315-321 ◽  
Author(s):  
O Skalli ◽  
M F Pelte ◽  
M C Peclet ◽  
G Gabbiani ◽  
P Gugliotta ◽  
...  

alpha-Smooth muscle (alpha-sm) actin, an isoform typical of smooth muscle cells (SMC) and present in high amounts in vascular SMC, was demonstrated in the cytoplasm of pericytes of various rat and human organs by means of immunocytochemistry at the electron microscopic level. In SMC and pericytes, alpha-sm actin was localized in microfilament bundles, strengthening the assumption that it is the functional isoform in these cell types and supporting the assumption that pericytes exert contractile functions.


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