Peripheral blood derived endothelial colony forming cells as suitable cell source for pre-endothelialization of arterial vascular grafts under dynamic flow conditions

Kraus, Xenia; Flierdt, Edda van de; Renzelmann, Jannis; Thoms, Stefanie; Witt, Martin; Scheper, Thomas; Blume, Cornelia

doi:10.1016/j.mvr.2022.104402

Cited by 10 publications

(3 citation statements)

References 72 publications

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“…It is well known that endothelial cells are constitutive part of vascular and consists of HUVECs and human aortic endothelial cells (HAECs). 52 Although we obtained substantial evidence showing that Neu5Ac was a risk factor for HUVECs function, the most widely used cell type during in vitro endothelial cell research, as well as involved in AS progression, the detailed function/ mechanism of Neu5Ac on HAECs still needs to be explored in the future.…”

Section: Discussionmentioning

confidence: 94%

N‐acetylneuraminic acid modulates SQSTM1/p62 sialyation‐mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice

Chen,

Qiu,

Chen

et al. 2023

IUBMB Life

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Sialic acid (SIA) has been reported to be a risk factor for atherosclerosis (AS) due to its high plasma levels in such patients. However, the effect of increasing SIA in circulation on endothelial function during AS progression remains unclear. In the present study, ApoE−/− mice and endothelial cells line (HUVEC cells) were applied to investigate the effect of SIA on AS progression and its potential molecular mechanism. In vivo, mice were injected intraperitoneally with Neu5Ac (main form of SIA) to keep high‐level SIA in circulation. ORO, H&E, and Masson staining were applied to detect the plaque progression. In vitro, HUVECs were treated with Neu5Ac at different times, CCK‐8, RT‐PCR, western blot, and immunoprecipitation methods were used to analyze its effects on endothelial function and the potential involved mechanism. Results from the present study showed that high plasma levels of Neu5Ac in ApoE−/− mice could aggravate the plaque areas as well as increase necrotic core areas and collagen fiber contents. Remarkably, Neu5Ac levels in circulation displayed a positive correlation with AS plaque areas. Furthermore, results from HUVECs showed that Neu5Ac inhibited cells viability in a time/dose‐dependent manner, by then induced the activation of inflammation makers such as ICAM‐1 and IL‐1β. Mechanism study showed that the activation of excessive autophagy medicated by SQSTM1/p62 displayed an important role in endothelium inflammatory injury. Neu5Ac could modify SQSTM1/p62 as a sialylation protein, and then increase its level with ubiquitin binding, further inducing ubiquitination degradation and being involved in the excessive autophagy pathway. Inhibition of sialylation by P‐3Fax‐Neu5Ac, a sialyltransferase inhibitor, reduced the binding of SQSTM1/p62 to ubiquitin. Together, these findings indicated that Neu5Ac increased SQSTM1/p62‐ubiquitin binding through sialylation modification, thereby inducing excessive autophagy and subsequent endothelial injury. Inhibition of SQSTM1/p62 sialylation might be a potential strategy for preventing such disease with high levels of Neu5Ac in circulation.

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Section: Discussionmentioning

confidence: 94%

N‐acetylneuraminic acid modulates SQSTM1/p62 sialyation‐mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice

Chen,

Qiu,

Chen

et al. 2023

IUBMB Life

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“…The findings of this brief co-culture study are promising for extended in vitro culture of multicellular TEVGs utilising the scaffold substrates engineered here. Further research is required into the optimisation of TEVG endothelialisation to develop a smooth, continuous surface resembling the native lumen, with studies into the effects of physiological flow conditions on luminal surface morphology [52].…”

Section: Discussionmentioning

confidence: 99%

Highly compliant biomimetic scaffolds for small diameter tissue-engineered vascular grafts (TEVGs) produced via melt electrowriting (MEW)

Weekes,

Wehr,

Pinto

et al. 2023

Biofabrication

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Biofabrication approaches toward the development of tissue-engineered vascular grafts (TEVGs) have been widely investigated. However, successful translation has been limited to large diameter applications, with small diameter grafts frequently failing due to poor mechanical performance, in particular mismatched radial compliance. Herein, melt electrowriting (MEW) of poly(ϵ-caprolactone) has enabled the manufacture of highly porous, biocompatible microfibre scaffolds with physiological anisotropic mechanical properties, as substrates for the biofabrication of small diameter TEVGs. Highly reproducible scaffolds with internal diameter of 4.0 mm were designed with 500 and 250 µm pore sizes, demonstrating minimal deviation of less than 4% from the intended architecture, with consistent fibre diameter of 15 ± 2 µm across groups. Scaffolds were designed with straight or sinusoidal circumferential microfibre architecture respectively, to investigate the influence of biomimetic fibre straightening on radial compliance. The results demonstrate that scaffolds with wave-like circumferential microfibre laydown patterns mimicking the architectural arrangement of collagen fibres in arteries, exhibit physiological compliance (12.9 ± 0.6% per 100 mmHg), while equivalent control geometries with straight fibres exhibit significantly reduced compliance (5.5 ± 0.1% per 100 mmHg). Further mechanical characterisation revealed the sinusoidal scaffolds designed with 250 µm pores exhibited physiologically relevant burst pressures of 1078 ± 236 mmHg, compared to 631 ± 105 mmHg for corresponding 500 µm controls. Similar trends were observed for strength and failure, indicating enhanced mechanical performance of scaffolds with reduced pore spacing. Preliminary in vitro culture of human mesenchymal stem cells validated the MEW scaffolds as suitable substrates for cellular growth and proliferation, with high cell viability (>90%) and coverage (>85%), with subsequent seeding of vascular endothelial cells indicating successful attachment and preliminary endothelialisation of tissue-cultured constructs. These findings support further investigation into long-term tissue culture methodologies for enhanced production of vascular extracellular matrix components, toward the development of the next generation of small diameter TEVGs.

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“…Recent advances in single-cell analysis and endothelial differentiation fostered a concept of therapeutic lymphangiogenesis, a treatment implying the guided regeneration of lymphatic networks upon the lymph node dissection to remove or ameliorate lymphoedema [16][17][18]. Isolation and culture of peripheral blood-derived, endothelial, colony-forming cells, which combine the molecular signatures of arterial, venous, and lymphatic ECs and have a high proliferation rate, significantly improved the development of tissue-engineered vascular grafts [19][20][21][22][23]. Hence, our knowledge of endothelial heterogeneity has been implemented into regenerative medicine and may be valuable for healthcare as soon as clinical trials of pre-endothelialised tissue-engineered vascular grafts or local treatment with autologous cells or angiogenic growth factors show their efficiency.…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

Frolov,

Lobov,

Kabilov

et al. 2023

IJMS

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Major adverse cardiovascular events occurring upon coronary artery bypass graft surgery are typically accompanied by endothelial dysfunction. Total arterial revascularisation, which employs both left and right internal thoracic arteries instead of the saphenous vein to create a bypass, is associated with better mid- and long-term outcomes. We suggested that molecular profiles of human coronary artery endothelial cells (HCAECs) and human internal mammary artery endothelial cells (HITAECs) are coherent in terms of transcriptomic and proteomic signatures, which were then investigated by RNA sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Both HCAECs and HITAECs overexpressed molecules responsible for the synthesis of extracellular matrix (ECM) components, basement membrane assembly, cell-ECM adhesion, organisation of intercellular junctions, and secretion of extracellular vesicles. HCAECs were characterised by higher enrichment with molecular signatures of basement membrane construction, collagen biosynthesis and folding, and formation of intercellular junctions, whilst HITAECs were notable for augmented pro-inflammatory signaling, intensive synthesis of proteins and nitrogen compounds, and enhanced ribosome biogenesis. Despite HCAECs and HITAECs showing a certain degree of molecular heterogeneity, no specific markers at the protein level have been identified. Coherence of differentially expressed molecular categories in HCAECs and HITAECs suggests synergistic interactions between these ECs in a bypass surgery scenario.

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Peripheral blood derived endothelial colony forming cells as suitable cell source for pre-endothelialization of arterial vascular grafts under dynamic flow conditions

Cited by 10 publications

References 72 publications

N‐acetylneuraminic acid modulates SQSTM1/p62 sialyation‐mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice

N‐acetylneuraminic acid modulates SQSTM1/p62 sialyation‐mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice

Highly compliant biomimetic scaffolds for small diameter tissue-engineered vascular grafts (TEVGs) produced via melt electrowriting (MEW)

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

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