Rebuilding the microenvironment of primary tumors in humans: a focus on stroma

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(3), С. 527 - 548

Опубликована: Март 5, 2024

Abstract Conventional tumor models have critical shortcomings in that they lack the complexity of human stroma. The heterogeneous stroma is a central compartment microenvironment (TME) must be addressed cancer research and precision medicine. To fully model stroma, deconstruction reconstruction tissues been suggested as new approaches for vitro modeling. In this review, we summarize heterogeneity tumor-associated stromal cells general used to isolate patient-specific from tissue; also address effect procedure on characteristics primary cells. Finally, perspectives future reconstructed are discussed, with an emphasis essential prerequisites developing authentic humanized models.

Язык: Английский

---

Novel tools to study cell-ECM interactions, cell adhesion dynamics and migration

Current Opinion in Cell Biology, Год журнала: 2024, Номер 88, С. 102355 - 102355

Опубликована: Апрель 16, 2024

Integrin-mediated cell adhesion is essential for migration, mechanotransduction and tissue integrity. In vivo, these processes are regulated by complex physicochemical signals from the extracellular matrix (ECM). These nuanced cues, including molecular composition, rigidity topology, call sophisticated systems to faithfully explore behaviour. Here, we discuss recent methodological advances in cell-ECM research compile a toolbox of techniques that expect shape this field future. We outline breakthroughs facilitating transition rigid 2D substrates more dynamic 3D systems, as well super-resolution imaging an in-depth understanding nanostructure. Selected methods exemplified with relevant biological findings underscore their applicability research. new "toolbox" will allow closer approximation vitro experimental setups vivo conditions, providing deeper insights into physiological pathophysiological associated adhesion.

Язык: Английский

---

Photo‐Responsive Decellularized Small Intestine Submucosa Hydrogels

Advanced Functional Materials, Год журнала: 2024, Номер 34(36)

Опубликована: Апрель 18, 2024

Abstract Decellularized small intestine submucosa (dSIS) is a promising biomaterial for promoting tissue regeneration. Isolated from the submucosal layer of animal jejunum, SIS rich in extracellular matrix (ECM) proteins, including collagen, laminin, and fibronectin. Following mild decellularization, dSIS becomes an acellular that supports cell adhesion, proliferation, differentiation. Conventional usually obtained by thermal crosslinking, which yields soft scaffold with low stability. To address these challenges, modified methacrylate groups photocrosslinking into stable hydrogels. However, has not been clickable handles orthogonal crosslinking. Here, development norbornene‐modified dSIS, named dSIS‐NB, via reacting amine carbic anhydride acidic aqueous reaction conditions reported. Using triethylamine (TEA) as base catalyst, high degrees NB substitution on are obtained. In addition to describing synthesis its adaptability hydrogel crosslinking cancer vascular engineering explored. Impressively, compared physically crosslinked collagen matrices, orthogonally dSIS‐NB hydrogels supported rapid dissemination cells superior vasculogenic angiogenic properties. also exploited versatile bioink 3D bioprinting.

Язык: Английский

---

3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Июнь 25, 2024

Abstract Cell spheroids (esp. organoids) as 3D culture platforms are popular models for representing cell–cell and cell–extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures natural tissues. with spatially organized multiple types preferred gaining comprehensive insights into tissue pathophysiology constructing in vitro tissues disease because of complexities In recent years, an assembly strategy using (or living building blocks has been developed to construct complex spatial organization. Here, a overview advances multispheroid studies is provided. The different mechanisms techniques, i.e., automated directed assembly, noncontact remote programmed self‐assembly, introduced. processing steps, advantages, technical limitations existing methodologies summarized. Applications strategies modeling, drug screening, engineering, organogenesis reviewed. Finally, this review concludes by emphasizing persistent issues future perspectives, encouraging researchers adopt techniques generating advanced that better resemble real

Язык: Английский

---

Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 3, 2025

Язык: Английский

---

Ablation of integrin-mediated cell–collagen communication alleviates fibrosis

Annals of the Rheumatic Diseases, Год журнала: 2023, Номер 82(11), С. 1474 - 1486

Опубликована: Июль 21, 2023

Activation of fibroblasts is a hallmark fibrotic processes. Besides cytokines and growth factors, are regulated by the extracellular matrix environment through receptors such as integrins, which transduce biochemical mechanical signals enabling cells to mount appropriate responses according biological demands. The aim this work was investigate in vivo role collagen-fibroblast interactions for regulating fibroblast functions fibrosis.Triple knockout (tKO) mice with combined ablation integrins α1β1, α2β1 α11β1 were created address significance integrin-mediated cell-collagen communication. Properties primary dermal lacking collagen-binding delineated vitro. Response tKO skin bleomycin induced challenge assessed.Triple integrin-deficient develop normally, transiently smaller reveal mild alterations mechanoresilience skin. Fibroblasts from these culture show defects cytoskeletal architecture, traction stress generation, production organisation. Ablation three leads increased levels discoidin domain receptor 2, an alternative recognising collagens However, overexpression fails compensate adhesion spreading on collagen substrates Mice severely attenuated response impaired mechanotransduction, reduced organisation.The data provide evidence crucial force generation differentiation vitro deposition tissue remodelling vivo. Targeting fibroblast-collagen might represent promising therapeutic approach regulate connective diseases.

Язык: Английский

---

A mechanosensitive caveolae–invadosome interplay drives matrix remodelling for cancer cell invasion

Nature Cell Biology, Год журнала: 2023, Номер 25(12), С. 1787 - 1803

Опубликована: Окт. 30, 2023

Invadosomes and caveolae are mechanosensitive structures that implicated in metastasis. Here, we describe a unique juxtaposition of caveola clusters matrix degradative invadosomes at contact sites between the plasma membrane cancer cells constricting fibrils both 2D 3D type I collagen environments. Preferential association straight segments fibrils, bent was observed along with remodelling. Caveola recruitment precedes is required for invadosome formation activity. Reciprocally, disruption results accumulation fibril-associated caveolae. Moreover, receptor β1 integrin co-localize integrins control to fibrils. In turn, mediate clearance uptake an invadosome-dependent collagen-cleavage-dependent mechanism. Our data reveal reciprocal interplay coordinates adhesion proteolytic remodelling confining support tumour cell dissemination.

Язык: Английский

---

Using Biosensors to Study Organoids, Spheroids and Organs-on-a-Chip: A Mechanobiology Perspective

Biosensors, Год журнала: 2023, Номер 13(10), С. 905 - 905

Опубликована: Сен. 24, 2023

The increasing popularity of 3D cell culture models is being driven by the demand for more in vivo-like conditions with which to study biochemistry and biomechanics numerous biological processes health disease. Spheroids organoids are platforms that self-assemble regenerate from stem cells, tissue progenitor cells or lines, show great potential studying development regeneration. Organ-on-a-chip approaches can be used achieve spatiotemporal control over biochemical biomechanical signals promote growth differentiation. These model systems engineered serve as disease drug screens. While methods have been developed support these structures, challenges remain completely recapitulate cell–cell cell–matrix interactions occurring vivo. Understanding how forces influence functions will require precise tools measure such forces, well a better understanding mechanobiology interactions. Biosensors prove powerful measuring both contexts, thereby leading mechanical at cellular levels. Here, we discussed biosensors mechanobiological research coupled develop accurate, physiologically relevant development, function, malfunction disease, avenues intervention.

Язык: Английский

---

Trends in 3D models of inflammatory bowel disease

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(3), С. 167042 - 167042

Опубликована: Янв. 29, 2024

Inflammatory bowel disease (IBD) encompasses a set of chronic inflammatory conditions, namely Crohn's and ulcerative colitis. Despite all advances in the management IBD, definitive cure is not available, largely due to lack holistic understanding its etiology pathophysiology. Several vitro, vivo, ex vivo models have been developed over past few decades order abbreviate remaining gaps. The establishment reliable predictable vitro intestinal inflammation may indeed provide valuable tools expedite validate development therapies for IBD. Three-dimensional (3D) more accurate representation different layers intestine, contributing stronger impact on drug screening research inflammation, bridging gap between research. This work provides critical overview state-of-the-art existing 3D discusses challenges, providing insights possible pathways towards achieving IBD mimetic models. We also address some main challenges faced by implementing cell culture while bearing mind clinical translational aspects.

Язык: Английский

---

Coordinated in confined migration: crosstalk between the nucleus and ion channel-mediated mechanosensation

Trends in Cell Biology, Год журнала: 2024, Номер 34(10), С. 809 - 825

Опубликована: Янв. 29, 2024

Язык: Английский

---