Machine Learning identifies remodeling patterns in human lung extracellular matrix.

Organ function depends on the three-dimensional integrity of the extracellular matrix (ECM). The structure resulting from the location and association of ECM components is a central regulator of cell behavior, but a dearth of matrix-specific analysis keeps it unresolved. Here, we deploy a high-resolution, 3D ECM mapping method and design a machine-learning powered pipeline to detect and characterize ECM architecture during health and disease.

Resolution of Acinar Dedifferentiation Regulates Tissue Remodeling in Pancreatic Injury and Cancer Initiation.

Background & Aims: Acinar-to-ductal metaplasia (ADM) is crucial in the development of pancreatic ductal adenocarcinoma. However, our understanding of the induction and resolution of ADM remains limited. We conducted comparative transcriptome analyses to identify conserved mechanisms of ADM in mouse and human.

In Situ Decellularization of Tissues Applied to the Topographical Analysis of Tumor-Associated Extracellular Matrix.

The extracellular matrix (ECM) is a network woven out of more than 1300 different proteins, of which ≈300 are structural. Their presence, distribution, and abundance change between and within tissues. It is also increasingly clear that the ECM is remodeled in disease-specific patterns.

Fibroblast-derived matrix models desmoplastic properties and forms a prognostic signature in cancer progression.

The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts.

Matritecture: Mapping the extracellular matrix architecture during health and disease.

All cells in multicellular organisms are housed in the extracellular matrix (ECM), an acellular edifice built up by more than a thousand proteins and glycans. Cells engage in a reciprocal relationship with the ECM; they build, inhabit, maintain, and remodel the ECM, while, in turn, the ECM regulates their behavior. The homeostatic balance of cell-ECM interactions can be lost, due to ageing, irritants or diseases, which results in aberrant cell behavior.

Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor.

Metastatic cancer spread is responsible for most cancer-related deaths. To colonize a new organ, invading cells adapt to, and remodel, the local extracellular matrix (ECM), a network of proteins and proteoglycans underpinning all tissues, and a critical regulator of homeostasis and disease. However, there is a major lack in tools to study cancer cell behavior within native 3D ECM.

Decellularization of the Murine Cardiopulmonary Complex.

We present here a decellularization protocol for mouse heart and lungs. It produces structural ECM scaffolds that can be used to analyze ECM topology and composition. It is based on a microsurgical procedure designed to catheterize the trachea and aorta of a euthanized mouse to perfuse the heart and lungs with decellularizing agents.

Basement membrane stiffness determines metastases formation.

The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores.

Author Correction: Decellularization and antibody staining of mouse tissues to map native extracellular matrix structures in 3D.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Decellularization and antibody staining of mouse tissues to map native extracellular matrix structures in 3D.

The extracellular matrix (ECM) is a major regulator of homeostasis and disease, yet the 3D structure of the ECM remains poorly understood because of limitations in ECM visualization. We recently developed an ECM-specialized method termed in situ decellularization of tissues (ISDoT) to isolate native 3D ECM scaffolds from whole organs in which ECM structure and composition are preserved. Here, we present detailed surgical instructions to facilitate decellularization of 33 different mouse tissues and details of validated antibodies that enable the visualization of 35 mouse ECM proteins.

ISDoT: in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix.

The extracellular matrix (ECM) is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Here we present a fast and efficient approach to enhance the study of ECM composition and structure.

The potential for targeting extracellular LOX proteins in human malignancy.

The extracellular matrix (ECM) is the physical scaffold where cells are organized into tissues and organs. The ECM may be modified during cancer to allow and promote proliferation, invasion, and metastasis. The family of lysyl oxidase (LOX) enzymes cross-links collagens and elastin and, therefore, is a central player in ECM deposition and maturation.

Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes.

Objective: To study vascular anatomy on oral cancer-draining lymph nodes before metastasis in mice.

Material And Methods: Cell lines: highly lymph metastatic oral squamous cell carcinoma SASL1m and non-metastatic human adenoid cystic carcinoma ACC2. Bone marrow transplants and xenografts: Nude mice were lethally irradiated and transplanted with bone marrow cells from EGFP(+) mice.

Maxillofacial intraoral distraction osteogenesis followed by elastic traction in cleft maxillary deformity.

We present a case of severe maxillary hypoplasia in a 16 years old cleft patient treated by distraction osteogenesis maxillary advancement. Initial evaluation showed vertical and antero-posterior maxillary deficiencies, and a Class III malocclusion. Two intraoral distractors (Zurich Pediatric Maxillary Distractor, KLS Martin, Tuttlingen, Germany) were placed in a high Le Fort I osteotomy.