Quantification and Statistical Analysis Methods for Vessel Wall Components from Stained Images with Masson's Trichrome

Hernández-Morera, Pablo; Castaño-González, Irene; González, Carmelo Javier León; Mompeó, Blanca; Ortega-Santana, Francisco

doi:10.1371/journal.pone.0146954

Cited by 30 publications

(15 citation statements)

References 25 publications

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“…tumor tissue has a fewer collagen-rich areas and disorganized collagen architecture compared to normal colon tissue. We obtained colon tissue biopsies from 12 healthy, 6 well differentiated (lowgrade), and 6 poorly differentiated (high-grade) CRC patients, and assessed the differences in the patterns of collagen-rich areas between healthy tumor tissues [26][27][28] . Trichrome staining of healthy tissue (Fig.…”

Section: Resultsmentioning

confidence: 99%

Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo

Devarasetty

Dominijanni

Herberg

et al. 2020

Sci Rep

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The tumor microenvironment (TME) plays a significant role in cancer progression and thus modeling it will advance our understanding of cancer growth dynamics and response to therapies. Most in vitro models are not exposed to intact body physiology, and at the same time, fail to recapitulate the extensive features of the tumor stroma. conversely, animal models do not accurately capture the human tumor architecture. We address these deficiencies with biofabricated colorectal cancer (cRc) tissue equivalents, which are built to replicate architectural features of biopsied cRc tissue. our data shows that tumor-stroma co-cultures consisting of aligned extracellular matrix (ECM) fibers and ordered micro-architecture induced an epithelial phenotype in cRc cells while disordered ecM drove a mesenchymal phenotype, similar to well and poorly differentiated tumors, respectively. Importantly, co-cultures studied in vitro, and upon implantation in mice, revealed similar tumor growth dynamics and retention of architectural features for 28 days. Altogether, these results are the first demonstration of replicating human tumor ecM architecture in ex vivo and in vivo cultures. Tumors are products of their environment. They send signals that can have significant effects on local tissue, and they receive signals from nearby cells and extracellular matrix (ECM) that can alter their progression 1-3. Despite the importance of a tumor's environment, current strategies for prognostication of tumors are centered around analyses of the tumor cells in isolation, such as morphological assessment or proliferative index calculation 4,5. Although these metrics are correlated to tumor progression, they do not capture the dynamics between a tumor and its surrounding space leading to inaccuracies when attempting to predict tumor progression and chemotherapeutic response 6,7. New technologies that improve prognostication will have a significant effect on patient mortality and lead to development of novel therapeutics which target and control tumor cells specifically, sparing healthy tissue from the deleterious effects of contemporary chemotherapeutics 8,9. Recent studies have identified the tumor microenvironment (TME) as a major contributing factor to cancer development and growth. The combination of paracrine factors, stromal cells such as endothelial, macrophages and tumor associated fibroblasts (TAFs), ECM proteins, and tissue mechanics coalesce into the perfect environment for a cancer to thrive and evade treatment 2,3. Of particular interest to our research: a number of studies have shown that tissue biomechanics 10-12 and ECM architectures 13,14 can alter and guide cancer cell phenotype, as well as alter therapeutic response. These findings indicate the TME as a potential target for innovative anti-cancer cell, or cancer-modulating, therapies. To devise TME targeting therapies, in vitro models of the TME need to be developed and validated. Many groups, including ours, have used tissue engineering techniques to fabricate tumor constructs that ...

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Section: Resultsmentioning

confidence: 99%

Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo

Devarasetty

Dominijanni

Herberg

et al. 2020

Sci Rep

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“…To qualitatively assess differences in the patterns of collagen-rich areas between healthy colon and CRC tissue, we performed trichrome staining. [18][19][20] We obtained colon tissue biopsies from 12 healthy, 6 low-grade, and 6 high-grade CRC patients. Healthy tissue ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Simulating the human tumor microenvironment in colorectal cancer organoids in vitro and in vivo

Devarasetty¹,

Dominijanni²,

Herberg

et al. 2019

Preprint

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The tumor microenvironment (TME) plays a significant role in cancer growth and metastasis. Bioengineered models of the TME will advance our understanding of cancer progression and facilitate identification of novel anti-cancer therapeutics that target TME components such as extracellular matrix (ECM) and stromal cells. However, most current in vitro models fail to recapitulate the extensive features of the human tumor stroma, especially ECM architecture, and are not exposed to intact body physiology. On the other hand, in vivo animal models do not accurately capture human tumor architecture. Using the features of biopsied colorectal cancer (CRC) tissue as a guide, we address these deficiencies by creating human organoids containing a colonic stromal ECM layer and CRC spheroids. Organoids were studied in vitro and upon implantation in mice for 28 days. We show that the stromal ECM micro-architecture, generated in vitro, was maintained in vivo for at least 28 days. Furthermore, comparisons with biopsied CRC tumors revealed that organoids with orderly structured TMEs induce an epithelial phenotype in CRC cells, similar to low-grade tumors, compared to a mesenchymal phenotype observed in disordered TMEs, similar to high-grade tumors. Altogether, these results are the first demonstration of replicating the human tumor ECM architecture in biofabricated tumor organoids under ex vivo and in vivo conditions.

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“…In fact, the venous systems structure follows a pattern in concentric layers: intima, media, and adventitia, which undergo a modification of structural components of the vessel wall in conditions of altered venous flow, associated to loss of tone and the subsequent venous dilatation [ 68 ]. The Masson’s trichrome stain revealed in red the smooth muscle fiber to smooth muscle fiber (SMF), while dyed bluish corresponded to the extracellular matrix (ECM), in which many elements such as collagen and elastin are arranged [ 69 ]. Some studies connected reflux with weakening of the venous walls, which may be due to an imbalance in the content of collagen and elastin in the vein [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The Inhibition of Prolyl Oligopeptidase as New Target to Counteract Chronic Venous Insufficiency: Findings in a Mouse Model

et al. 2020

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(1) Background: Chronic venous insufficiency (CVI) is a common disorder related to functional and morphological abnormalities of the venous system. Inflammatory processes and angiogenesis alterations greatly concur to the onset of varicose vein. KYP-2047 is a selective inhibitor of prolyl oligopeptidase (POP), a serine protease involved in the release of pro-angiogenic molecules. The aim of the present study is to evaluate the capacity of KYP-2047 to influence the angiogenic and inflammatory mechanisms involved in the pathophysiology of CVI. (2) Methods: An in vivo model of CVI-induced by saphene vein ligation (SVL) and a tissue block culture study were performed. Mice were subjected to SVL followed by KYP-2047 treatment (intraperitoneal, 10 mg/kg) for 7 days. Histological analysis, Masson’s trichrome, Van Gieson staining, and mast cells evaluation were performed. Release of cytokines, nitric oxide synthase production, TGF-beta, VEGF, α-smooth muscle actin, PREP, Endoglin, and IL-8 quantification were investigated. (3) Results: KYP-2047 treatment ameliorated the histological abnormalities of the venous wall, reduced the collagen increase and modulated elastin content, lowered cytokines levels and prevented mast degranulation. Moreover, a decreased expression of TGF-beta, eNOS, VEGF, α-smooth muscle actin, IL-8, and PREP was observed in in vivo study; also a reduction in VEGF and Endoglin expression was confirmed in tissue block culture study. (4) Conclusions: For the first time, this research, highlighting the importance of POP as new target for vascular disorders, revealed the therapeutic potential of KYP-2047 as a helpful treatment for the management of CVI.

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Quantification and Statistical Analysis Methods for Vessel Wall Components from Stained Images with Masson's Trichrome

Cited by 30 publications

References 25 publications

Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo

Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo

Simulating the human tumor microenvironment in colorectal cancer organoids in vitro and in vivo

The Inhibition of Prolyl Oligopeptidase as New Target to Counteract Chronic Venous Insufficiency: Findings in a Mouse Model

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