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Enhancing Cell-Based Regenerative Therapies with Peptide-Modified Thermo-responsive Citrate-Based Biomaterials for Treatment of Critical Limb Ischemia

ABSTRACT: Enhancing Cell-Based Regenerative Therapies with Peptide-Modified Thermo-responsive Citrate-Based Biomaterials for Treatment of Critical Limb Ischemia

PROVIDER: PRJNA1098778 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28621300.fastq.gz	Fastqsanger.gz
	SRR28621301.fastq.gz	Fastqsanger.gz
	SRR28621302.fastq.gz	Fastqsanger.gz
	SRR28621303.fastq.gz	Fastqsanger.gz
	SRR28621304.fastq.gz	Fastqsanger.gz

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Enhancing Cell-Based Regenerative Therapies with Peptide-Modified Thermo-responsive Citrate-Based Biomaterials for Treatment of Critical Limb Ischemia

Project description:Critical limb ischemia (CLI) poses a significant health challenge, marked by severe morbidity and limited treatment options leading to high mortality rates. Despite the promise of cell-based therapy, challenges such as poor cell survival and engraftment during and after cell delivery hinder its efficacy. This study explores the potential of peptide-modified thermo-responsive citrate-based biomaterials as carriers for endothelial cell delivery to promote vascular regeneration in CLI. Specifically, various pro-survival peptides were covalently tethered to poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to investigate their effect on the delivery of vascular endothelial cells to skeletal muscle tissue. After screening with in vitro and in vivo experiments, laminin-derived peptide A5G81 and VEGF-derived peptide QK were identified to promote endothelial cell spreading, proliferation, and prolonged cell survival when tethered onto PPCN The viscoelastic properties of PPCN provided protection against shear stress induced cell death during injection, while the peptides regulated endothelial cell behavior via distinct molecular pathways. Importantly, intramuscular delivery of endothelial cells with PPCN-A5G81 and PPCN-QK in a murine hindlimb ischemia model resulted in significant improvements in limb perfusion, tissue preservation and functional outcomes. Furthermore, endothelial cell delivery with PPCN-A5G81 and PPCN-QK also promoted positive skeletal muscle remodeling following ischemic injury. These findings underscore the potential of bioactive materials as novel cell delivery carriers for CLI therapy, with implications for advancing regenerative therapeutics and revolutionizing CLI treatment strategies.

2024-04-12 | GSE263721 | GEO

Selective autophagic degradation of ATP citrate lyase maintains citrate homeostasis and promotes oocyte maturation

Project description:Autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects the oocyte maturation. Here, we show a clear tendency of reduced autophagy level in human granulosa cell from women of advanced maternal age, implying a potential negative correlation between autophagy level and oocyte quality. We therefore established a co-culture system and show that either pharmacological inhibition or genetic ablation of autophagy in granulosa cells negatively affect the oocyte quality and fertilization ability. Moreover, our metabolomics analysis indicates that the adverse impact of autophagy impairment on oocyte quality is mediated by downregulated citrate levels, while exogenous supplementation of citrate can significantly restore the oocyte maturation. In molecular level, we found ATP citrate lyase (Acly), which is a crucial enzyme catalyzing the cleavage of citrate, was preferentially associated with K63-linked ubiquitin chains and recognized by the autophagy receptor protein SQSTM1/p62 for the selective autophagic degradation. In human follicles, autophagy levels in granulosa cells was downregulated with maternal aging, accompanied by decreased citrate in the follicular fluid, implying a potential correlation between citrate metabolism and oocyte quality. We also show that elevated citrate levels in porcine follicular fluid promote oocyte maturation. Collectively, our data reveal that autophagy in granulosa cells is a beneficial mechanism to maintain a certain degree of citrate by selectively targeting Acly during oocyte maturation.

2023-01-09 | GSE190697 | GEO

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering.

Project description:Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering.

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citrate vs nitrate Reducing cultures

Project description:The effect of nitrate reduction (anaerobic cultivation in the presence of heme, vitamin K2 and nitrate) was compared with anaerobic cultivation supplemented with citrate (Lactobacillus plantarum). The medium was chemically defined medium with mannitol as main carbon source Two-condition experiment, nitrate vs citrate reducing cells. Biological replicates: 4 nitrate reducing cultures, 4 citrate reducing cultures, independently grown and harvested. Two slides were used, each slide contained 8 Arrays. Citrate reducing cultures are called reactor 1-4, Nitrate reducing cultures are called reactor A-D

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2020-12-31 | GSE26570 | GEO

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2023-02-01 | PXD033621 | Pride

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2019-12-03 | MSV000084653 | MassIVE

Ureibacillus thermosphaericus str. Thermo-BF

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Mitochondrial citrate metabolism and efflux regulates trophoblast differentiation

Project description:Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation. In this work, we employed static and stable isotope tracing untargeted metabolomics methods together with gene expression and histone acetylation studies in an established cell culture model of trophoblast differentiation. Trophoblast differentiation was associated with increased abundance of the TCA cycle intermediates citrate and α-ketoglutarate. Citrate was preferentially exported from mitochondria in the undifferentiated state but was retained to a larger extent within mitochondria upon differentiation. Correspondingly, differentiation was associated with decreased expression of the mitochondrial citrate transporter (CIC). CRISPR/Cas9 disruption of the mitochondrial citrate carrier showed that CIC is required for biochemical differentiation of trophoblast. Loss of CIC resulted in broad alterations in gene expression and histone acetylation. These gene expression changes were partially rescued through acetate supplementation. Taken together, these results highlight a central role for mitochondrial citrate metabolism in the orchestration of histone acetylation and gene expression during trophoblast differentiation.

2023-05-05 | GSE223514 | GEO

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