Functional role of glycosaminoglycans in decellularized lung extracellular matrix

Uhl, Franziska E.; Zhang, Fuming; Pouliot, Robert A.; Uriarte, Juan J.; Enes, Sara Rolandsson; Han, Xianlin; Ouyang, Yilan; Xia, Ke; Westergren‐Thorsson, Gunilla; Malmström, Anders; Hällgren, Oskar; Linhardt, Robert J.; Weiss, Daniel J.

doi:10.1016/j.actbio.2019.11.029

Cited by 73 publications

(53 citation statements)

References 51 publications

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“…Glycosaminoglycans (GAGs) are linear acidic heteropolysaccharides that exist in all mammals and are formed by repeating disaccharide units composed of N-acetyl-hexosamine and hexuronic or hexose ( Table 1; Vasconcelos and Pomin, 2017). GAGs can have different sulfation patterns with different charge densities and heterogeneous monosaccharide compositions (Uhl et al, 2020). In addition to HA, GAGs are synthesized from the Golgi apparatus in the form of proteoglycans (Sasarman et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins

Jin

2021

Front. Mol. Biosci.

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Glycosaminoglycans (GAGs) constitute a considerable fraction of the glycoconjugates found on cellular membranes and in the extracellular matrix of virtually all mammalian tissues. The essential role of GAG-protein interactions in the regulation of physiological processes has been recognized for decades. However, the underlying molecular basis of these interactions has only emerged since 1990s. The binding specificity of GAGs is encoded in their primary structures, but ultimately depends on how their functional groups are presented to a protein in the three-dimensional space. This review focuses on the application of NMR spectroscopy on the characterization of the GAG-protein interactions. Examples of interpretation of the complex mechanism and characterization of structural motifs involved in the GAG-protein interactions are given. Selected families of GAG-binding proteins investigated using NMR are also described.

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Section: Introductionmentioning

confidence: 99%

NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins

Jin

2021

Front. Mol. Biosci.

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“…So far, hydrogels have been by far the most produced and studied substrate, where ECM-based hydrogels from murine, porcine and human tissues have been developed with different decellularization methods. In order to mimic the natural tissue when designing an artificial matrix, it is vital to maintain the components of the ECM, often measured as the GAG-DNA content ratio, as well as the viscoelastic properties ( Uhl et al, 2020 ). Apart from hydrogels based on decellularized tissue, there are various natural, synthetic and hybrid (meaning combining natural, synthetic or ECM components) polymers that are being explored, including proteins, polysaccharides, recombinantly expressed peptides, and polyethylene glycol ( Uhl et al, 2020 ).…”

Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

“…In order to mimic the natural tissue when designing an artificial matrix, it is vital to maintain the components of the ECM, often measured as the GAG-DNA content ratio, as well as the viscoelastic properties ( Uhl et al, 2020 ). Apart from hydrogels based on decellularized tissue, there are various natural, synthetic and hybrid (meaning combining natural, synthetic or ECM components) polymers that are being explored, including proteins, polysaccharides, recombinantly expressed peptides, and polyethylene glycol ( Uhl et al, 2020 ). The advantage of hydrogels is that the structural properties can be easily modified through the crosslinking of the hydrophilic polymer chains.…”

Section: Modulating the 3d Environment For Treatmentmentioning

confidence: 99%

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

et al. 2021

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It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal stromal/stem cells (MSC) have been shown to have immunomodulatory properties and may be potent actors regulating tissue remodelling and regenerative cell responses upon lung injury. Using MSC in cell-based therapy holds promise for treatment of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, so far clinical trials with MSCs in COPD have not had a significant impact on disease amelioration nor on IPF, where low cell survival rate and pulmonary retention time are major hurdles to overcome. Research shows that the microenvironment has a profound impact on transplanted MSCs. In our studies on acellular lung tissue slices (lung scaffolds) from IPF patients versus healthy individuals, we see a profound effect on cellular activity, where healthy cells cultured in diseased lung scaffolds adapt and produce proteins further promoting a diseased environment, whereas cells on healthy scaffolds sustain a healthy proteomic profile. Therefore, modulating the environmental context for cell-based therapy may be a potent way to improve treatment using MSCs. In this review, we will describe the importance of the microenvironment for cell-based therapy in chronic lung diseases, how MSC-ECM interactions can affect therapeutic output and describe current progress in the field of cell-based therapy.

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“…The lung is a very complex mechanical organ composed of various cell types and ECM components [7]. The degradation of proteoglycans and their GAGs after the decellularisation process is an important observation that might be one of the explanations behind the lack of proper cell repopulation and tissue functionality [4,6,8]. GAGs are known to be involved in ECM organisation and assembly, as well as in remodelling processes during normal homeostasis [9].…”

Section: Challenges and Opportunities In The Field: Where Do We Stand?mentioning

confidence: 99%

Bioartificial lungs based on de- and recellularisation approaches: a historical perspective

Enes

Weiss

2020

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Functional role of glycosaminoglycans in decellularized lung extracellular matrix

Cited by 73 publications

References 51 publications

NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins

NMR Characterization of the Interactions Between Glycosaminoglycans and Proteins

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

Bioartificial lungs based on de- and recellularisation approaches: a historical perspective

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