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

Cause and consequence of heterogeneity in human mesenchymal stem cells: Challenges in clinical application DOI
Zhao Lyu,

Miaomiao Xin,

Dale Reece Oyston

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155354 - 155354

Published: May 15, 2024

Language: Английский

Citations

32
Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations DOI Creative Commons
Si Chen,

Bowei Liang,

Jianyong Xu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 15, 2024

Mesenchymal stem/stromal cells (MSCs) represent a heterogeneous cell population distributed throughout various tissues, demonstrating remarkable adaptability to microenvironmental cues and holding immense promise for disease treatment. However, the inherent diversity within MSCs often leads variability in therapeutic outcomes, posing challenges clinical applications. To address this heterogeneity, purification of MSC subpopulations through marker-based isolation has emerged as promising approach ensure consistent efficacy. In review, we discussed reported markers MSCs, encompassing those developed candidate marker strategies high-throughput approaches, with aim explore viable addressing heterogeneity illuminate prospective research directions field.

Language: Английский

Citations

18
Single‐Cell and Spatial Transcriptomics Decodes Wharton's Jelly‐Derived Mesenchymal Stem Cells Heterogeneity and a Subpopulation with Wound Repair Signatures DOI
Penghong Chen, Shijie Tang, Ming Li

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 10(4)

Published: Dec. 11, 2022

Abstract The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ‐MSCs) may be responsible for the poor clinical outcomes and reproducibility treatments based on WJ‐MSCs. Exploration WJ‐MSC heterogeneity with multimodal single‐cell technologies will aid in establishing accurate MSC subtyping developing screening protocols dominant functional subpopulations. Here, WJ‐MSCs are systematically analyzed by single cell spatial transcriptome sequencing. Single‐cell transcriptomics analysis identifies four subpopulations, namely proliferative_MSCs, niche‐supporting_MSCs, metabolism‐related_MSCs biofunctional‐type_MSCs. Furthermore, transcriptome, cellular heterogeneity, cell‐state trajectories these subpopulations characterized. Intriguingly, biofunctional‐type MSCs (marked S100A9, CD29, CD142) selected this study exhibit promising wound repair properties vitro vivo. Finally, integrating omics data, it has been found that S100A9 + CD29 CD142 subpopulation is more enriched fetal segment umbilical cord, suggesting deriving from have potential into an ideal therapeutic agent healing. Overall, presented comprehensively maps provides essential resource future development WJ‐MSC‐based drugs.

Language: Английский

Citations

42
Wharton’s jelly mesenchymal stem cells: a concise review of their secretome and prospective clinical applications DOI Creative Commons

Hana Drobiova,

Sardar Sindhu,

Rasheed Ahmad

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 27, 2023

Accumulating evidence indicates that most primary Wharton’s jelly mesenchymal stem cells (WJ-MSCs) therapeutic potential is due to their paracrine activity, i.e., ability modulate microenvironment by releasing bioactive molecules and factors collectively known as secretome. These can either be released directly into the surrounding or embedded within membrane-bound extracellular nano-sized (usually 30–150 nm) messenger particles vesicles of endosomal origin with specific route biogenesis, exosomes carried relatively larger (100 nm–1 μm) formed outward blebbing plasma membrane called microvesicles (MVs); MVs are (EVs). The found in secretome various types, including cytokines, chemokines, cytoskeletal proteins, integrins, growth factors, angiogenic mediators, hormones, metabolites, regulatory nucleic acid molecules. As expected, performs different biological functions, such immunomodulation, tissue replenishment, cellular homeostasis, besides possessing anti-inflammatory anti-fibrotic effects. This review highlights current advances research on WJ-MSCs’ its prospective clinical applications.

Language: Английский

Citations

23
Advances and applications of biomimetic biomaterials for endogenous skin regeneration DOI Creative Commons
Mengyang Wang, Yiyue Hong, Xiaobing Fu

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 39, P. 492 - 520

Published: May 30, 2024

Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials inducing endogenous skin are simplistic in their structure function, lacking ability to accurately mimic intricate tissue regulate disordered microenvironment. Novel biomimetic with precise structure, chemical composition, biophysical properties offer a promising avenue achieving perfect regeneration. Here, we outline recent advances materials induced from aspects structural functional mimicry, physiological process regulation, property design. Furthermore, novel techniques including situ reprograming, flexible electronic skin, artificial intelligence, single-cell sequencing, spatial transcriptomics, which have contribute development highlighted. Finally, prospects challenges further research application discussed. This review provides reference address clinical problems rapid high-quality

Language: Английский

Citations

10
Development and experimental validation of a machine learning-based disulfidptosis-related ferroptosis score for hepatocellular carcinoma DOI
Cong Zhang, Tiantian Xu,

Kun Ji

et al.

APOPTOSIS, Journal Year: 2023, Volume and Issue: 29(1-2), P. 103 - 120

Published: Oct. 24, 2023

Language: Английский

Citations

18
Advancements in Spinal Cord Injury Repair: Insights from Dental-Derived Stem Cells DOI Creative Commons
Xueying Wen, Wenkai Jiang, Xiaolin Li

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 683 - 683

Published: March 19, 2024

Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts growing interest in stem cell therapy as promising avenue for treatment. Dental-derived cells, including dental pulp cells (DPSCs), from human exfoliated deciduous teeth (SHED), the apical papilla (SCAP), follicle (DFSCs), are of due to their accessibility, minimally invasive extraction, robust differentiating capabilities. Research indicates potential differentiate into neural promote SCI repair animal models at both tissue functional levels. This review explores applications dental-derived repair, covering transplantation, conditioned culture medium injection, bioengineered delivery systems, exosomes, extracellular vesicle treatments, combined therapies. Assessing clinical effectiveness treatment SCI, further research is necessary. includes investigating biological mechanisms conducting Large-animal studies trials. It also important undertake more comprehensive comparisons, optimize selection types, implement functionalized system. These efforts will enhance therapeutic repairing SCI.

Language: Английский

Citations

7
Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease DOI Creative Commons

Shulin Wei,

Mingxing Li, Qin Wang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 3307 - 3334

Published: May 1, 2024

Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory of the gastrointestinal tract, which has high recurrence rate and incurable due to lack effective treatment. Mesenchymal stromal cells (MSCs) are class pluripotent stem that have recently received lot attention their strong self-renewal ability immunomodulatory effects, large number experimental clinical models confirmed positive therapeutic effect MSCs on IBD. In preclinical studies, MSC treatment for IBD relies paracrine cell-to-cell contact, its mediated mitochondrial transfer immune regulation. It also plays role in restoring intestinal mucosal barrier through homing effect, regulation microbiome, repair epithelial cells. latest trials, safety efficacy been by transfusion autologous or allogeneic bone marrow, umbilical cord, adipose MSCs, as well derived extracellular vesicles. However, regarding stable use several concerns emerge, including cell sources, management (dose, route frequency administration, pretreatment MSCs) adverse reactions. This article comprehensively summarizes effects mechanisms advantages over conventional drugs, trial progress The current challenges future directions discussed. review would add knowledge into understanding applying MSCs. Keywords: mesenchymal cells, immunomodulation, disease, ulcerative colitis, Crohn's therapy

Language: Английский

Citations

7
Application progress of single-cell sequencing technology in mesenchymal stem cells research DOI Creative Commons
Hao Li, Yusong Wang, Gehua Zhu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 9, 2024

Single-Cell Sequencing (SCS) technology plays an important role in the field of Mesenchymal Stem Cells (MSCs) research. This paper comprehensively describes application SCS MSCs research, including (1) enables more precise characterization and biomarker definition. (2) reveals prevalent gene expression heterogeneity among different subclusters within MSCs, which contributes to a comprehensive understanding function diversity developmental, regenerative, pathological contexts. (3) provides insights into dynamic transcriptional changes experienced by during differentiation complex web signaling pathways regulatory factors controlling key processes proliferation, regulation, interactions mechanisms. (4) The analytical methods underpinning data are rapidly evolving converging with histological research systematically deconstruct functions mechanisms MSCs. review new perspectives for unraveling biological properties, heterogeneity, potential, functions, clinical potential at single-cell level.

Language: Английский

Citations

6
HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures DOI Creative Commons

Zhian Chen,

Tianhua Zhou, Huan Luo

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 12, 2024

Abstract The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate release mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role tissue regeneration. This study aimed verify whether MSC-EVs promote damage repair mediated by MFs and explore mechanisms. In vitro experiments showed human umbilical cord Wharton’s jelly (hWJMSC-EVs) promoted vitality chondrocytes proliferation differentiation ability bone marrow-derived MSCs. was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), MSCs overexpress ITGB1 after absorbing EVs, thereby activating transforming growth factor-β/Smad2/3 axis. a rabbit knee joint model osteochondral defect repair, injection different concentrations into cavity concentration 50 µg/ml significantly improved formation transparent MF surgery. Extraction regenerated revealed changes ITGB1, factor-β, Smad2/3 were directly proportional cartilage. summary, Graphical abstract

Language: Английский

Citations

6