Development of an In Vitro Biomimetic Peripheral Neurovascular Platform

Malheiro, Afonso; Seijas‐Gamardo, Adrián; Harichandan, Abhishek; Mota, Carlos; Wieringa, Paul; Moroni, Lorenzo

doi:10.1021/acsami.2c03861

Cited by 10 publications

(5 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various 3D cell models have been developed to study vasculature in vitro 29,30 , however, the analysis of endothelial structures has been performed mainly from 2D projections. Here, we used automated 3D segmentation to analyze the endothelial sprout morphology.…”

Section: Discussionmentioning

confidence: 99%

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space

Beter

Abdollahzadeh

Pulkkinen

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Three-dimensional image analyses are required to improve the understanding of the regulation of blood vessel formation and heterogeneity. Currently, quantitation of 3D endothelial structures or vessel branches is often based on 2D projections of the images losing their volumetric information. Here, we developed SproutAngio, a Python-based open-source tool, for fully automated 3D segmentation and analysis of endothelial lumen space and sprout morphology. To test the SproutAngio, we produced a publicly available in vitro fibrin bead assay dataset with a gradually increasing VEGF-A concentration (https://doi.org/10.5281/zenodo.7240927). We demonstrate that our automated segmentation and sprout morphology analysis, including sprout number, length, and nuclei number, outperform the widely used ImageJ plugin. We also show that SproutAngio allows a more detailed and automated analysis of the mouse retinal vasculature in comparison to the commonly used radial expansion measurement. In addition, we provide two novel methods for automated analysis of endothelial lumen space: (1) width measurement from tip, stalk and root segments of the sprouts and (2) paired nuclei distance analysis. We show that these automated methods provided important additional information on the endothelial cell organization in the sprouts. The pipelines and source code of SproutAngio are publicly available (https://doi.org/10.5281/zenodo.7381732).

show abstract

Section: Discussionmentioning

confidence: 99%

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space

Beter

Abdollahzadeh

Pulkkinen

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Primary SCs were obtained from the sciatic nerves of neonatal rat pups according to a previous study [96,97]. In brief, the collected sciatic nerve segments were sliced and digested in 5 ml of 0.1% II collagenase solution and 5 ml of 0.25% trypsin solution for 45 min at 37 °C and 5% CO2.…”

Section: Purification and Culture Of Primary Scsmentioning

confidence: 99%

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Sun,

Zeng,

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

Background Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI. Results We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation. Conclusion This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair. Graphical Abstract

show abstract

“…Neurovascular tissue forms congruent patterns, whose three-dimension structure established vital interactions between neural and vascular tissue 43 . In the process of nerve regeneration, angiogenesis plays a signi cant role in assisting nerve repair 44,45 .…”

Section: Vascular Related Eldsmentioning

confidence: 99%

Transcriptome analysis of Long non-coding RNAs altered in sciatic nerves of aging SD rats

Kuang

Zhang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objectives To investigate the long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) changes in the sciatic nerve (SN) in Sprague Dawley (SD) rats during aging. Methods Eighteen healthy SD rats were selected at the age of 1 month (1M) and 24 months (24M) and SNs were collected. High-throughput transcriptome sequencing and bioinformatics analysis were performed. Protein-protein interaction (PPI) networks and competing endogenous RNA (ceRNA) networks were established according to differentially expressed genes (DEGs). Result As length of lncRNAs increased, its proportion to the total number of lncRNAs decreased. A total of 4079 DElncRNAs were identified in Con vs 24M. GO analysis were primarily clustered in nerve and lipid metabolism, extracellular matrix, and vascularization related fields. There were 17 nodes in the PPI network of the target genes of up-regulating genes including Itgb2, Lox, Col11a1, Wnt5a, Kras, etc. Using quantitative RT-PCR, microarray sequencing accuracy was validated. And there were 169 nodes constructing the PPI network of down-regulated target genes, mainly including Col1a1, Hmgcs1, Hmgcr. CeRNA interaction networks were constructed. Conclusion Lipid metabolism, angiogenesis and ECM fields might play an important role in senescence process in SNs. Col3a1, Serpinh1, Hmgcr, Fdps could be candidates for nerve aging research.

show abstract

Development of an In Vitro Biomimetic Peripheral Neurovascular Platform

Cited by 10 publications

References 80 publications

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis

Transcriptome analysis of Long non-coding RNAs altered in sciatic nerves of aging SD rats

Contact Info

Product

Resources

About