Glycans and hybrid glyco-materials for artificial cell microenvironment fabrication

Pignatelli, Cataldo; Cadamuro, F.; Magli, Sofia; Rossi, Lorenzo; Russo, Laura; Nicotra, Francesco

doi:10.1039/9781788013864-00250

Cited by 2 publications

(5 citation statements)

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“…Moreover, they are further activated by TGFβ1 autocrine signaling, which elicits a harmful self-sustaining mechanism [68]. In healthy conditions, type I and type III collagen fibrils are present and confer structural thickness and stiffness to the ECM [69]. Collagen fibril assembly is favored by crosslinks between lysine residues through a process catalyzed by extracellular enzyme lysyl-oxidases (LOX) [70].…”

Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

“…Fibrillar collagen type I is one of the molecules most involved in desmoplasia [73]. Additionally, type IV collagen and laminin are part of the basement membrane and are similarly over synthetized, causing modifications in the architecture of the surrounding microenvironment [69,[74][75][76]. Particularly, laminin proteins appear to be ubiquitously distributed within the stroma, creating a discontinuous basement membrane [77].…”

Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

“…HA has been largely investigated in PDAC, since it is overexpressed in neoplastic and stromal cells [82]. HA is a polysaccharide and non-sulfated GAG component of ECM, characterized by important viscoelastic properties and involved in the water uptake of tissues [17,68,69,83,84]. Its receptor, CD44, leads to the activation of different intracellular signaling pathways, including the PI3K-AKT ERK, RhoA and RAS pathways, thereby promoting cell survival, invasion and epithelial-to-mesenchymal transition [85,86].…”

Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

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The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options

Ferrara¹,

Pignatelli²,

Cossutta

et al. 2021

Cancers

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The stroma is a relevant player in driving and supporting the progression of pancreatic ductal adenocarcinoma (PDAC), and a large body of evidence highlights its role in hindering the efficacy of current therapies. In fact, the dense extracellular matrix (ECM) characterizing this tumor acts as a natural physical barrier, impairing drug penetration. Consequently, all of the approaches combining stroma-targeting and anticancer therapy constitute an appealing option for improving drug penetration. Several strategies have been adopted in order to target the PDAC stroma, such as the depletion of ECM components and the targeting of cancer-associated fibroblasts (CAFs), which are responsible for the increased matrix deposition in cancer. Additionally, the leaky and collapsing blood vessels characterizing the tumor might be normalized, thus restoring blood perfusion and allowing drug penetration. Even though many stroma-targeting strategies have reported disappointing results in clinical trials, the ECM offers a wide range of potential therapeutic targets that are now being investigated. The dense ECM might be bypassed by implementing nanoparticle-based systems or by using mesenchymal stem cells as drug carriers. The present review aims to provide an overview of the principal mechanisms involved in the ECM remodeling and of new promising therapeutic strategies for PDAC.

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Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

Section: Fibrosis and Ecm Remodeling Affect Pancreatic Microenvironmentmentioning

confidence: 99%

See 1 more Smart Citation

The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options

Ferrara¹,

Pignatelli²,

Cossutta

et al. 2021

Cancers

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“…Physiologically, the ECM provides mechanical and physical support to cells and affects cell migration, proliferation, and differentiation ( 50 , 51 ). It is a three-dimensional network composed of fibrous-forming proteins, such as collagens, laminins, glycoproteins, elastin, and glycosaminoglycans ( 51 , 52 ). In the pancreas, BM is predominant: it surrounds the acinar cells of the exocrine pancreas, duct vessels, and pancreatic islets ( 53 ).…”

Section: The Endocrine Nichementioning

confidence: 99%

“…This evidence supports the idea that ECM components play beneficial roles towards endocrine pancreatic cells. In conclusion, the ECM was originally thought to exist to solely provide structural support to cells and it is now recognized as a reservoir of information contributing to tissue homeostasis and function ( 51 ).…”

Section: The Endocrine Nichementioning

confidence: 99%

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

Pignatelli¹,

Campo

Neroni

et al. 2022

Transpl Int

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Intrahepatic islet transplantation is a promising β-cell replacement strategy for the treatment of type 1 diabetes. Instant blood-mediated inflammatory reactions, acute inflammatory storm, and graft revascularization delay limit islet engraftment in the peri-transplant phase, hampering the success rate of the procedure. Growing evidence has demonstrated that islet engraftment efficiency may take advantage of several bioengineering approaches aimed to recreate both vascular and endocrine compartments either ex vivo or in vivo. To this end, endocrine pancreas bioengineering is an emerging field in β-cell replacement, which might provide endocrine cells with all the building blocks (vascularization, ECM composition, or micro/macro-architecture) useful for their successful engraftment and function in vivo. Studies on reshaping either the endocrine cellular composition or the islet microenvironment have been largely performed, focusing on a single building block element, without, however, grasping that their synergistic effect is indispensable for correct endocrine function. Herein, the review focuses on the minimum building blocks that an ideal vascularized endocrine scaffold should have to resemble the endocrine niche architecture, composition, and function to foster functional connections between the vascular and endocrine compartments. Additionally, this review highlights the possibility of designing bioengineered scaffolds integrating alternative endocrine sources to overcome donor organ shortages and the possibility of combining novel immune-preserving strategies for long-term graft function.

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Glycans and hybrid glyco-materials for artificial cell microenvironment fabrication

Cited by 2 publications

References 0 publications

The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options

The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

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