Deciphering decidual deficiencies in recurrent spontaneous abortion and the therapeutic potential of mesenchymal stem cells at single-cell resolution DOI Creative Commons

Beibei Jin,

Xiaoying Ding,

Jiamin Dai

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 29, 2024

Abstract Background Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis treatment have yet to be studied in detail. In recent years, Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) been shown effective treating various diseases. Current understanding RSA using WJ-MSCs limited, exact mechanisms action remains largely unclear. this study, we explored decidual deficiencies therapeutic potential at single-cell resolution. Methods Three mouse models were established: normal pregnancy group, an WJ-MSC group. Decidual tissue samples collected for RNA sequencing (scRNA-seq) functional verification, including resolution situ hybridization on tissues (SCRINSHOT) immunofluorescence. Results We generated atlas from pregnant, RSA, WJ-MSC-treated mice identified 14 cell clusters decidua day 14. Among these populations, stromal most abundant decidua, further three novel subclusters (Str_0, Str_1, Str_2). also demonstrated IL17 TNF signaling pathways enriched upregulated DEGs mice. Intriguingly, cell–cell communication analysis revealed Str_1 cell-related gene expression was greatly reduced group rescued Notably, interaction between NK other attenuated, Spp1 (identified as endometrial toleration-related marker) significantly could restored by treatment. Conclusion Herein, implemented scRNA-seq systematically evaluate cellular heterogeneity transcriptional regulatory networks associated with WJ-MSCs. These data targets remodel subpopulations provided new insights into decidua-derived developmental defects maternal–foetal interface.

Language: Английский

Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses DOI Creative Commons
Chuanyuan Wei, Wei Sun,

Kangjie Shen

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 8, 2023

Abstract Acral melanoma (AM) is a rare subtype of characterized by high incidence lymph node (LN) metastasis, critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell spatial transcriptomic analyses to investigate the dynamic evolution early AM dissemination. Our findings reveal substantial inter- intra-tumor heterogeneity AM, alongside highly immunosuppressive microenvironment complex intercellular communication networks, particularly patients with LN metastasis. Notably, identify strong association between MYC + Melanoma ( MEL) FGFBP2 NKT cells Furthermore, demonstrate that metastasis requires metabolic shift towards fatty acid oxidation (FAO) induced MITF MEL cells. Etomoxir, clinically approved FAO inhibitor, can effectively suppress MITF-mediated This comprehensive dataset enhances our understanding provides insights into potential targeting for management

Language: Английский

Citations

13
Exosomes from mesenchymal stem cells: Potential applications in wound healing DOI Creative Commons

Sicheng Li,

Yichuan Li,

Kèyù Zhü

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 357, P. 123066 - 123066

Published: Sept. 19, 2024

Language: Английский

Citations

5
Unveiling the functional heterogeneity of cytokine-primed human umbilical cord mesenchymal stem cells through single-cell RNA sequencing DOI Creative Commons
Zhiwei Hu,

Duanduan Li,

Shiduo Wu

et al.

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 26, 2024

Mesenchymal stem cells (MSCs) hold immense promise for use in immunomodulation and regenerative medicine. However, their inherent heterogeneity makes it difficult to achieve optimal therapeutic outcomes a specific clinical disease. Primed MSCs containing certain cytokine can enhance particular functions, thereby increasing potential related diseases. Therefore, understanding the characteristic changes underlying mechanisms of primed by various cytokines is highly important. In this study, we aimed reveal cellular heterogeneity, functional subpopulations, molecular with IFN-γ, TNF-α, IL-4, IL-6, IL-15, IL-17 using single-cell RNA sequencing (scRNA-seq). Our results demonstrated that priming minimized MSC transcriptome, while expression surface markers exhibited only slight changes. Notably, compared IL-17; IL-4 priming, which stimulated significantly greater number differentially expressed genes (DEGs). Functional analysis, included Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses, indicated IL-4-primed hUC-MSCs are involved interferon-mediated immune-related processes, leukocyte migration, chemotaxis potential, extracellular matrix cell adhesion, respectively. Moreover, an investigation biological function scores IFN-γ-primed exhibit strong immunomodulatory ability, TNF-α-primed high express elevated amounts collagen. Finally, observed alters distribution subpopulations MSCs, these functions. Taken together, our study revealed distinct regulatory effects on function, at level. These findings contribute comprehensive inflammatory paving way precise treatment applications.

Language: Английский

Citations

4
cGAMP-targeting injectable hydrogel system promotes periodontal restoration by alleviating cGAS-STING pathway activation DOI
Xiang Liu, Hua Zhang, Lei Xu

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 48, P. 55 - 70

Published: Feb. 13, 2025

Language: Английский

Citations

0
Comparative analysis of transcriptomic profiles of mesenchymal stem cells at the onset of senescence and after exposure to acute exogenous oxidative stress DOI Creative Commons
Zozo Outskouni,

Stella Prapa,

Andreas Goutas

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 754, P. 151506 - 151506

Published: Feb. 20, 2025

Language: Английский

Citations

0
Advancing diabetes treatment: the role of mesenchymal stem cells in islet transplantation DOI Creative Commons
Lisha Mou,

Tony Bowei Wang,

Xinyu Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 28, 2024

Diabetes mellitus, a prevalent global health challenge, significantly impacts societal and economic well-being. Islet transplantation is increasingly recognized as viable treatment for type 1 diabetes that aims to restore endogenous insulin production mitigate complications associated with exogenous dependence. We review the role of mesenchymal stem cells (MSCs) in enhancing efficacy islet transplantation. MSCs, characterized by their immunomodulatory properties differentiation potential, are seen valuable graft survival, reducing immune-mediated rejection, supporting angiogenesis tissue repair. The utilization MSC-derived extracellular vesicles further exemplifies innovative approaches improve outcomes. However, challenges such MSC heterogeneity optimization therapeutic applications persist. Advanced methodologies, including artificial intelligence (AI) single-cell RNA sequencing (scRNA-seq), highlighted potential technologies addressing these challenges, potentially steering therapy toward more effective, personalized modalities diabetes. This revealed MSCs important advancing strategies, particularly through highlights importance field regenerative medicine, acknowledging both must be navigated fully realize promise.

Language: Английский

Citations

3
Innovative treatment of age-related hearing loss using MSCs and EVs with Apelin DOI Creative Commons

Shengqun Xu,

Dongliang Liu, Fang Zhang

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Jan. 17, 2025

Utilizing single-cell transcriptome sequencing (scRNA-seq) technology, this study explores the viability of employing mesenchymal stem cells (MSCs) as a therapeutic approach for age-related hearing loss (ARHL). The research demonstrates MSCs' ability to differentiate into inner ear cell subpopulations, particularly hair cells, delivering Apelin via extracellular vesicles (EVs) promote M2 macrophage polarization. In vitro experiments show reduced inflammation and preservation health. elderly mice, MSCs transplantation leads regeneration, restoring auditory function. These findings highlight regenerative capabilities EV-mediated approaches ARHL.

Language: Английский

Citations

0
Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice DOI Creative Commons
Jiacheng Shen, Li Wu, Xiaoying Shi

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 5, 2024

Abstract Background Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) demonstrated unprecedented potential in treatment POF. However, heterogeneity human UC-MSCs remains challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within that possess capability improve function, with aim reducing uncertainty arising from while achieving more effective Methods 10 × Genomics was performed investigate UC-MSCs. We used LRP1 as marker distinguished therapeutic subpopulation by flow cytometry, determined its secretory functions. Unsorted UC-MSCs, high low transplanted under capsules aged mice CTX-induced POF mice, effects evaluated assessing hormone levels, estrous cycles, follicle counts, embryo numbers. RNA sequencing mouse oocytes granulosa after explore mechanism cells. Results identified three distinct functional subtypes, including cells, multilymphoid progenitor trophoblasts. Additionally, we subpopulation, which improved function mice. elucidated unique functions capable secreting various chemokines, cytokines, growth factors. Furthermore, plays crucial role regulating microenvironment, tissue repair extracellular matrix remodeling. Consistent functions, transcriptomes revealed improves modulating oocytes, NAD metabolism, mitochondrial Conclusion Through exploration improving factors remodeling matrix. This study provides new insights into targeted precise Graphical abstract

Language: Английский

Citations

2
A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction DOI Creative Commons
Xicheng Wang, Chao Yang, Xiaoxue Ma

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 18, 2024

Background Treatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have therapeutic efficacy still in a low yield. Therefore, it is crucial to increase the production find novel ways assess MSCs. Materials methods hUC-MSCs were cultured 3-dimensional (3D) expansion system for obtaining enough clinical use, named as 3D A post-MI HF mouse model was employed conduct vivo vitro experiments. Single-cell bulk RNA-seq analyses performed on total 125 combination algorithms leveraged screen core ligand genes. Shinyapp shinycell workflows used deploying web-server. Result can significantly stably reduce extent HF. To understand stable potential cardioprotective mechanism, scRNA-seq revealed heterogeneity division-of-labor mode at cellular level. Specifically, scissor phenotypic analysis identified reported wound-healing CD142 + subpopulation that also associated cardiac protection ability - proliferative state, contributing function self-renewal, respectively. Differential expression conducted differentially expressed ligand-related achieved by employing algorithms. The present study developed machine learning predictive based 13 ligands. Further using CellChat demonstrated stronger secretion capacity compared Flow cytometry sorting qRT-PCR validation confirmed significant upregulation these factors Conclusion Clinical could serve cell product. Using data, we clarified functional subpopulation, which cooperatively contributed self-renewal maintenance MSCs, “division labor” Moreover, robustly predicting secretory user-friendly web-server constructed available ( https://wangxc.shinyapps.io/3D_MSCs/ ).

Language: Английский

Citations

2
The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles DOI Creative Commons

Yinhua Song,

Jiachen Wu, Yang Liu

et al.

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 27, 2024

Abstract Premature ovarian insufficiency (POI) is an essential cause of reduced fertility and quality life in young women. Mesenchymal stem cells (MSCs) MSCs-derived extracellular vesicles (EVs) have the ability to migrate damaged tissues are considered as promising therapeutic approaches for POI. However, homing efficacy MSCs administered vivo still insufficient, their potential tumorigenicity multi-differentiation also bring many doubts about safety. The targeting migration efficiency can be improved by genetic engineering surface modification, thereby maximizing efficacy. use viral vectors has increased safety concerns. In addition, EVs, which seem current alternative MSCs, poorly targeted distribution, although they terms This paper reviews comparative effects derived EVs on POI, biodistribution after administration, most important possible strategies. Difficulties such homogeneity yield before clinical application discussed. article will provide new insights into precision therapy drug delivery female diseases. Graphical

Language: Английский

Citations

2