Donor age significantly influences the Raman spectroscopic biomolecular fingerprint of human pancreatic extracellular matrix proteins following collagenase-based digestion

Spiers, R M; Marzi, Julia; Brauchle, Eva-Maria; Cross, Sarah E.; Vaughan, R H; Bateman, Paul A.; Hughes, Stephen J.; Schenke‐Layland, Katja; Prv., Johnson

doi:10.1016/j.actbio.2019.09.013

Cited by 17 publications

(11 citation statements)

References 58 publications

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“…During this process, collagenases are infused into the tissues, disrupting the interstitial matrix of fibrillar proteins, such as collagen type 1 (COL1). [4][5][6] The process partially digests the double basement membrane (BM) surrounding the islets, which is composed of collagen type 4 (COL4), laminins (LAM), fibronectin (FN), and proteoglycans. 6,7 BM proteins were reported to be differentially affected by the isolation procedure; perlecan and laminin a5 are completely lost, while COL4 and other LAM are still present after the process.…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] The process partially digests the double basement membrane (BM) surrounding the islets, which is composed of collagen type 4 (COL4), laminins (LAM), fibronectin (FN), and proteoglycans. 6,7 BM proteins were reported to be differentially affected by the isolation procedure; perlecan and laminin a5 are completely lost, while COL4 and other LAM are still present after the process. 7 The resulting loss in ECM structure has been previously shown to negatively impact islet survival and function of posttransplantation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Collagen and Endothelial Cell Coculture Improves β-Cell Functionality and Rescues Pancreatic Extracellular Matrix

Zbinden

Urbanczyk

Layland

et al. 2021

Tissue Engineering Part A

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The use of biomaterials and biomaterial functionalization is a promising approach to support pancreatic islet viability posttransplantation in an effort to reduce insulin dependence for patients afflicted with diabetes mellitus type 1. Extracellular matrix (ECM) proteins are known to impact numerous reparative functions in the body. Assessing how endogenously expressed pancreatic ECM proteins are affected by posttransplant-like hypoxic conditions may provide significant insights toward the development of tissue-engineered therapeutic strategies to positively influence b-cell survival, proliferation, and functionality. Here, we investigated the expression of three relevant groups of pancreatic ECM proteins in human native tissue, including basement membrane (BM) proteins (collagen type 4 [COL4], laminins [LAM]), proteoglycans (decorin [DCN], nidogen-1 [NID1]), and fibril-forming proteins (fibronectin [FN], collagen type 1 [COL1]). In an in vitro hypoxia model, we identified that ECM proteins were differently affected by hypoxic conditions, contributing to an overall loss of b-cell functionality. The use of a COL1 hydrogel as carrier material demonstrated a protective effect on bcells mitigating the effect of hypoxia on proteoglycans as well as fibril-forming protein expression, supporting b-cell functionality in hypoxia. We further showed that providing endothelial cells (ECs) into the COL1 hydrogel improves b-cell response as well as the expression of relevant BM proteins. Our data show that b-cells benefit from a microenvironment composed of structure-providing COL1 with the incorporation of ECs to withstand the harsh conditions of hypoxia. Such hydrogels support b-cell survival and can serve as an initial source of ECM proteins to allow cell engraftment while preserving cell functionality posttransplantation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Collagen and Endothelial Cell Coculture Improves β-Cell Functionality and Rescues Pancreatic Extracellular Matrix

Zbinden

Urbanczyk

Layland

et al. 2021

Tissue Engineering Part A

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show abstract

“…Previously, we reported that different types of collagens showed distinctive peaks related to CH 2 deformation at 1,453 and 1,456 cm −1 . 30 Intriguingly, Cc6, a protein-like component, was detected only in murine and human aTAA regions ( Figures 4 and 6 ). The spectrum of Cc6 features high intensities of several amino acid residues, indicating compositional changes of collagen molecules.…”

Section: Discussionmentioning

confidence: 94%

“… 25 , 26 In previous studies, Raman microspectroscopy was shown to reveal differences between healthy and cancerous tissues in the skin 27 , 28 and lungs, 29 and age-dependent differences in the ECM surrounding pancreatic islets. 30 Moreover, Raman microspectroscopy and Raman imaging have the potential to analyze cardiovascular ECM structures on a molecular level. 31 , 32 , 33 At this time, no reports are available regarding the assessment of aortic aneurysm by Raman measurements.…”

Section: Introductionmentioning

confidence: 99%

Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms

Sugiyama

Marzi

Alber

et al. 2021

Cell Reports Medicine

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“…Furthermore, single spectra (n=100/image) were extracted from the lipid-assigned regions for in-depth analysis of the molecular composition via principal component analysis (PCA) performed in The Unscambler X (Camo Analytics AS, Oslo, Norway). The application of PCA for the analysis of spectral data has been described elsewhere [28]. In brief, principal component (PC) score values were compared between the two groups to identify differences in their molecular composition.…”

Section: Methodsmentioning

confidence: 99%

FH loss in RPE cells causes retinal degeneration in a human RPE-porcine retinal explant co-culture model

Armento

Murali

Marzi

et al. 2021

Preprint

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Age-related Macular degeneration (AMD) is a degenerative disease of the macula affecting the elderly population. Treatment op-tions are limited, partly due to the lack of understanding of AMD pathology and the sparse availability of research models, that replicate the complexity of the human macula and the intricate interplay of the genetic, aging and life-style risk factors contrib-uting to AMD. One of the main genetic risks associated with AMD is located on Complement Factor H (CFH) gene, leading to an amino acid substitution in the FH protein (Y402H). However, the mechanism of how this FH variant promotes the onset of AMD remains unclear. Previously, we have shown that FH deprivation in RPE cells, via CFH silencing, leads to increased inflammation, metabolic impairment and vulnerability towards oxidative stress. In this study, we established a novel co-culture model comprised of CFH silenced RPE cells and porcine retinal explants derived from the visual streak of the porcine eyes, closely resembling the human macula. We show that retinae exposed to FH-deprived RPE cells show signs of retinal degeneration, with rod cells being the first cells to undergo degeneration. Moreover, via Raman analyses, we observe that the main changes involve the mitochondria and lipid composition of the co-cultured retinae upon FH loss. Interestingly, the detrimental effects of FH loss in RPE cells on the neuroretina were independent of glial cell activation and external complement sources. Moreover, we show that the co-culture model is also suitable for human retinal explants, and we observed a similar trend when RPE cells deprived of FH were co-cultured with human retinal explants from a single donor eye. Our findings highlight the importance of RPE derived FH for retinal homeostasis and provide a valuable model for AMD research.

show abstract

Donor age significantly influences the Raman spectroscopic biomolecular fingerprint of human pancreatic extracellular matrix proteins following collagenase-based digestion

Cited by 17 publications

References 58 publications

Collagen and Endothelial Cell Coculture Improves β-Cell Functionality and Rescues Pancreatic Extracellular Matrix

Collagen and Endothelial Cell Coculture Improves β-Cell Functionality and Rescues Pancreatic Extracellular Matrix

Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms

FH loss in RPE cells causes retinal degeneration in a human RPE-porcine retinal explant co-culture model

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