Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications

Hu, Xi-Min; Zhang, Qi; Zhou, Rui-Xin; Wu, Yanlin; Li, Zhixin; Zhang, Dan-Yi; Yang, Yichao; Yang, Ronghua; Hu, Yongjun; Xiong, Kun

doi:10.4252/wjsc.v13.i5.386

Cited by 22 publications

(13 citation statements)

References 253 publications

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“…This result is consistent with the result obtained by Wu et al who indicated a high level of IL-4, IL-17, and IFN-γ in animal models with the PopB and curdlan adjuvant compared to the control group (37). Moreover, our result was consistent with Hu et al, showing that TLR4 was crucial in host resistance to P. aeruginosa, and its deficiency led to increased polymorphonuclear (PMN) infiltration and pro-inflammatory cytokine production and a susceptible phenotype (52).…”

Section: Discussionsupporting

confidence: 93%

Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Sabzehali

Goudarzi

Chirani

et al. 2021

Arch Clin Infect Dis

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Background: The emerging problem of antibiotic resistance in Pseudomonas aeruginosa is a global health concern; hence, revealing innovative therapeutic approaches (such as designing an immunogenic vaccine candidate) is needed. There is no evidence of the availability of an effective vaccine that can combat the infection caused by this microorganism. Objectives: This research was conducted to develop a potential chimeric vaccine against P. aeruginosa using reverse vaccinology approaches. Methods: The present vaccine candidate comprised outer membrane protein F and I (OprF/OprI) and PopB with appropriate linkers. After applying meticulous immune-informatics investigation, the multi-epitope vaccine was created, including helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), interferon gamma (IFN-γ), and interleukin 4 (IL-4) epitopes. Then, the physicochemical characteristics, allergenicity, toxicity, and antigenicity were analyzed. After investigating the secondary structure, the tertiary structure (3D) model was generated, refined, and validated via computational methods. Besides, the strong protein-ligand interaction and stability between the vaccine candidate and toll-like receptor 4 (TLR4) were determined via molecular docking and dynamics analyses. Moreover, in silico cloning accompanied by pET-22b (+) was used to achieve high translation efficiency. Results: Our results presumed that the chimeric-designed vaccine was thermostable and contained optimal physicochemical properties. This vaccine candidate was nontoxic and highly soluble and had stable protein and TLR4 interaction, adequately overexpressed in Escherichia coli. Overall, it could induce immune responses and repress this microorganism. Conclusions: Therefore, to inhibit Pseudomonas infections experimentally, the efficacy and safety of the vaccine design need to be validated.

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Section: Discussionsupporting

confidence: 93%

Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Sabzehali

Goudarzi

Chirani

et al. 2021

Arch Clin Infect Dis

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“…Necroptosis is a proinflammatory lytic form of cell death with programmed properties occurring in numerous cells, including ADSCs. The signaling of this kind of programmed cell death is modulated by receptor-interacting protein kinase (RIP) 1 (RIP1), RIP3, and mixed lineage kinase domain-like pseudokinase (MLKL) when the activity of caspase-8 becomes compromised [ 12 ]. Following oxygen-glucose deprivation (OGD) treatment, the occurrence of necroptosis has been verified in hippocampal neurons, cardiomyocytes, endothelial cells, hepatocytes, and retinal ganglion cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of RIP3 increased ADSC viability under OGD and modified the competency of adipogenesis, angiogenesis, and inflammation regulation

Yang

et al. 2022

Bioscience Reports

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Adipose-derived stem cells (ADSCs) showed decreased cell viability and increased cell death under oxygen-glucose deprivation (OGD). Meanwhile, vital necroptotic proteins, including receptor-interacting protein kinase (RIP) 3 and mixed lineage kinase domain-like pseudokinase (MLKL), were expressed in the early stage. This study aims to explore the effect of necroptosis inhibition on ADSCs. ADSCs were obtained from normal human subcutaneous fat and verified by multidirectional differentiation and flow cytometry. By applying CCK8, calcein/PI staining and immunostaining, we determined the OGD treatment time of 4 hours, a timepoint when the cells showed a significant decrease in viability and increased protein expression of RIP3, phosphorylated RIP3 (pRIP3) and phosphorylated MLKL (pMLKL). After pretreatment with the inhibitor of RIP3, necroptotic protein expression decreased under OGD conditions, and cell necrosis decreased. Transwell assays proved that cell migration ability was retained. Furthermore, the expression of the adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and quantitative analysis of oil red O staining increased in the inhibitor group. The expression of vascular endothelial growth factor-A (VEGFA) and fibroblast growth factor 2 (FGF2) and the migration test suggest that OGD increases the secretion of vascular factors, promotes the migration of human umbilical vein endothelial cells (HUVECs), and forms unstable neovascularization. ELISA revealed that inhibition of RIP3 increased the secretion of the anti-inflammatory factor IL-10 and reduced the expression of the proinflammatory factor IL-1β. Inhibition of RIP3 can reduce the death of ADSCs, retain their migration ability and adipogenic differentiation potential, reduce unstable neovascularization and inhibit the inflammatory response.

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“…On the other hand, the terms related to positive regulation of programmed cell death (GO:0043068), extracellular matrix organisation (GO:0030198) and positive regulation of vesicle-mediated transport (GO:0060627) were among the enriched terms for downregulated mRNAs. Several previous studies have shown the link between programmed cell death and stem cells (Cheung et al, 2012; Ho et al, 2017; Hu et al, 2021). It might be particularly required during hESC differentiation to maintain the genomic integrity.…”

Section: Resultsmentioning

confidence: 99%

“…were among the enriched terms for downregulated mRNAs. Several previous studies have shown the link between programmed cell death and stem cells (Cheung et al, 2012;Ho et al, 2017;Hu et al, 2021). It might be particularly required during hESC differentiation to maintain the genomic integrity.…”

Section: Enrichment Analysesmentioning

confidence: 99%

Deciphering the mRNA-lncRNA-miRNA interaction landscape in human pluripotency

Ghosh

Som

2022

Preprint

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Human embryonic stem cells offer a huge potential for the study of early human development and for application in biomedical sciences. Growing evidence has shown that besides the protein coding genes, the non-coding elements of the human genome play a crucial role in maintaining its property of self renewal and in cell fate determination. However, a clear understanding of this regulatory mechanism and the landscape of interactions between the coding and non-coding elements was still lacking. To fill in this void, we use transcriptomic data from RNA-seq and small RNA-seq experiments to reconstruct the core pluripotency circuitry involving mRNAs, lncRNAs and miRNAs. The overall interaction landscape revealed an alternate circuit for the maintenance of pluripotency devoid of the classic pluripotency transcription factors NANOG, SOX2 and POU5F1. We also identified networks specific to the naive and primed states of human pluripotency revealing a new set of transcriptomic markers that could not only be used to differentiate pluripotent state from non-pluripotent state but also to identify the intra-pluripotency state. The lncRNA DANT1 was found to be crucial in determination to the two pluripotency states as it formed a bridge between the naive and primed state specific pluripotency networks. Further, we also identified and computationally validated putative ceRNA mechanism involving DANT1, the miRNAs hsa-miR-30c-2-3p, hsa-miR-210-3p and hsa-let-7b-5p, and several key pluripotency related genes including PTPRZ1, SALL2, TOX3, ZNF695, and ZYG11A which warrants further experimental validation.

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Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications

Cited by 22 publications

References 253 publications

Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

Inhibition of RIP3 increased ADSC viability under OGD and modified the competency of adipogenesis, angiogenesis, and inflammation regulation

Deciphering the mRNA-lncRNA-miRNA interaction landscape in human pluripotency

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