Stem Cells International
 Journal metrics
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Acceptance rate30%
Submission to final decision101 days
Acceptance to publication24 days
CiteScore8.800
Journal Citation Indicator0.820
Impact Factor5.131

Article of the Year 2021

Combined Use of Chitosan and Olfactory Mucosa Mesenchymal Stem/Stromal Cells to Promote Peripheral Nerve Regeneration In Vivo

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 Journal profile

Stem Cells International publishes papers in all areas of stem cell biology and applications. The journal publishes basic, translational, and clinical research, including animal models and clinical trials.

 Editor spotlight

Chief Editor Professor Li has a background in cardiac stem cell transplantation, using young stem cells to promote tissue repair following injury to rejuvenate the aged individual, and the development of biomaterials that can easily integrate into damaged heart tissue.

 Special Issues

We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

Latest Articles

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Research Article

Exosomes Derived from microRNA-27a-3p Overexpressing Mesenchymal Stem Cells Inhibit the Progression of Liver Cancer through Suppression of Golgi Membrane Protein 1

Hepatocellular carcinoma (HCC) remains a significant health burden to date. Its early diagnosis and treatment are complicated by the lack of early diagnosis markers and multidrug resistance. microRNA regulation of HCC oncogenes are among the new diagnostic and therapeutic strategies being explored, although the mode of delivery of a therapeutic dose of the miRNA remains a challenge. In this study, we explored the use of exosomes from umbilical mesenchymal stem cells transfected with miR-27a-3p to interact with the oncogene GOLM1 in HCC and inhibit HCC progression both in vitro and in vivo. We first determined and compared the expression levels of miR-27a-3p in blood, various cell lines and tissues of HCC and their corresponding normal controls. We then employed bioinformatics analysis to determine the gene target for miR-27a-3p in HCC and later transfected upregulated miR-27a-3p in mesenchymal stem cells, and treated HCC cells with exosomes extracted from the transfected stem cells. We then created mouse models of HCC using balbc/nude mice and equally treated them with exosomes from miR-27a-3p transfected stem cells. The results showed that miR-27a-3p is downregulated in blood, cell lines, and tissues of HCC patients compared to normal controls. Exosomes from the miR-27a-3p transfected mesenchymal stem cells prevented HCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Upregulation of miR-27a-3p prevented HCC through interacting with and downregulating GOLM1 as its target oncogene. In conclusion, miR-27a-3p is a potential therapeutic target for HCC acting through GOLM1.

Research Article

Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells

Hyperuricemia is a metabolic disorder that is essential to the development of inflammatory gout, with increasing prevalence over recent years. Emerging clinical findings has evidenced remarkable tendon damage in individuals with longstanding asymptomatic hyperuricemia, yet the impact of hyperuricemia on tendon homeostasis and associated repercussions is largely unknown. Here, we investigated whether asymptomatic hyperuricemia was associated with spontaneous ruptures in the Achilles tendon and the pathological effect of hyperuricemia on the tendon stem/progenitor cells (TSPCs). Significantly higher serum uric acid (SUA) levels were found in 648 closed Achilles tendon rupture (ATR) patients comparing to those in 12559 healthy volunteers. In vitro study demonstrated that uric acid (UA) dose dependently reduced rat Achilles TSPC viability, decreased the expressions of tendon collagens, and deformed their structural organization while significantly increased the transcript levels of matrix degradative enzymes and proinflammatory factors. Consistently, marked disruptions in Achilles tendon tissue structural and functional integrity were found in a rat model of hyperuricemia, together with enhanced immune cell infiltration. Transcriptome analysis revealed a significant elevation in genes involved in metabolic stress and tissue degeneration in TSPCs challenged by hyperuricemia. Specifically, reduced activity of the AKT-mTOR pathway with enhanced autophagic signaling was confirmed. Our findings indicate that asymptomatic hyperuricemia may be a predisposition of ATR by impeding the normal functions of TSPCs. This information may provide theoretical and experimental basis for exploring the early prevention and care of ATR.

Research Article

Long Noncoding RNA and mRNA m6A Modification Analyses of Periodontal Ligament Stem Cells from the Periodontitis Microenvironment Exposed to Static Mechanical Strain

Periodontal ligament stem cells (PDLSCs) play important roles in orthodontic tooth movement (OTM) and can respond to mechanical stress. Our previous study demonstrated that periodontal ligament stem cells derived from periodontitis tissue (pPDLSCs) are more sensitive to static mechanical strain (SMS) than those derived from healthy tissue (hPDLSCs) and reported the long noncoding RNA (lncRNA) expression profiles of pPDLSCs exposed to SMS. An increasing number of lncRNAs have been reported by various studies to be associated with the osteogenic differentiation of mesenchymal stem cells. Many studies have demonstrated that the n6-methyladenosine (m6A) modification exerts important effects on lncRNA and mRNA regulation of cell behaviors. However, the regulatory effects of lncRNA and mRNA m6A modification on PDLSCs have not been studied. Therefore, we performed an m6A microarray assay with pPLDSCs and hPDLSCs exposed to 12% SMS and found that 143 lncRNAs and 739 mRNAs were differentially methylated. These RNAs were thought to be involved in multiple differentiation and inflammatory responses. Moreover, we found that METTL3, an essential protein in the m6A system, was expressed at lower levels in the strain-exposed pPDLSCs than in strain-exposed hPLDSCs, and METTL3 promoted the osteogenic differentiation of pPDLSCs.

Research Article

Oral Cancer Stem Cell-Derived Small Extracellular Vesicles Promote M2 Macrophage Polarization and Suppress CD4+ T-Cell Activity by Transferring UCA1 and Targeting LAMC2

Cancer-derived small extracellular vesicles (sEVs) are emerging as crucial mediators of intercellular communication between cancer cells and M2-tumor-associated macrophages (M2-TAMs) via transferring lncRNAs. We previously reported that miR-134 blocks the expression of its targeting protein LAMC2 via the PI3K/AKT pathway and inhibits cancer stem cell (CSC) migration and invasion in oral squamous cell carcinoma (OSCC). This study hypothesize that OSCC-CSC-derived small extracellular vesicles (OSCC-CSC-sEVs) transfer a ceRNA of miR-134 and consequently promote M2 macrophage polarization by targeting LAMC2 via the PI3K/AKT pathway through in vitro and in vivo experiment methods. The results showed that sEVs derived from CD133+CD44+ OSCC cells promoted M2 polarization of macrophages by detecting several M2 macrophage markers (CD163, IL-10, Arg-1, and CD206+CD11b+). Mechanistically, we revealed that the lncRNA UCA1, by binding to miR-134, modulated the PI3K/AKT pathway in macrophages via targeting LAMC2. Importantly, OSCC-CSC-sEV transfer of UCA1, by targeting LAMC2, promoted M2 macrophage polarization and inhibited CD4+ T-cell proliferation and IFN-γ production in vitro and in vivo. Functionally, we demonstrated that M2-TAMs, by transferring exosomal UCA and consequently targeting LAMC2, enhanced cell migration and invasion of OSCC in vitro and the tumorigenicity of OSCC xenograft in nude mice. In conclusion, our results indicated that OSCC-CSC-sEV transfer of UCA1 promotes M2 macrophage polarization via a LAMC2-mediated PI3K/AKT axis, thus facilitating tumor progression and immunosuppression. Our findings provide a new understanding of OSCC-CSC molecular mechanisms and suggest a potential therapeutic strategy for OSCC through targeting CSC-sEVs and M2-TAMs.

Research Article

Exosomes Derived from Runx2-Overexpressing BMSCs Enhance Cartilage Tissue Regeneration and Prevent Osteoarthritis of the Knee in a Rabbit Model

Objectives. Osteoarthritis is the leading disease of joints worldwide. Osteoarthritis may be treated by exosomes derived from Runx2-overexpressed bone marrow mesenchymal stem cells (R-BMSCs-Exos). R-BMSCs-Exos would promote the proliferation, migration, and phenotypic maintenance of articular chondrocytes. Methods. BMSCs were transfected with and without Runx2. Exosomes derived from BMSCs and R-BMSCs (BMSCs-Exos and R-BMSCs-Exos) were isolated and identified. Proliferation, migration, and phenotypic maintenance were determined in vitro and compared between groups. The mechanism for activation of Yes-associated protein (YAP) was investigated using small interfering RNA (siRNA). The exosomes’ preventive role was determined in vivo using Masson trichrome and immunohistochemical staining. Results. R-BMSCs-Exos enhance the proliferation, migration, and phenotypic maintenance of articular chondrocytes based on the YAP being activated. R-BMSCs-Exos prevent knee osteoarthritis as studied in vivo through a rabbit model. Conclusions. Findings emphasize the efficacy of R-BMSCs-Exos in preventing osteoarthritis. Potential source of exosomes is sorted out for the advantages and shortcomings. The exosomes are then modified based on the molecular mechanisms to address their limitations. Such exosomes derived from modified cells have the role in future therapeutics.

Research Article

Xeno-Free Integrated Platform for Robust Production of Cardiomyocyte Sheets from hiPSCs

Human induced pluripotent stem cells (hiPSCs) can be efficiently differentiated into cardiomyocytes (CMs), which can be used for cardiac disease modeling, for drug screening, and to regenerate damaged myocardium. Implementation of xeno-free culture systems is essential to fully explore the potential of these cells. However, differentiation using xeno-free adhesion matrices often results in low CM yields and lack of functional CM sheets, capable of enduring additional maturation stages. Here, we established a xeno-free CM differentiation platform using TeSR/Synthemax, including a replating step and integrated with two versatile purification/enrichment metabolic approaches. Results showed that the replating step was essential to reestablish a fully integrated, closely-knit CM sheet. In addition, replating contributed to increase the cTnT expression from 65% to 75% and the output from 2.2 to 3.1 CM per hiPSC, comparable with the efficiency observed when using TeSR/Matrigel. In addition, supplementation with PluriSin1 and Glu-Lac+ medium allowed increasing the CM content over 80% without compromising CM sheet integrity or functionality. Thus, this xeno-free differentiation platform is a reliable and robust method to produce hiPSC-derived CMs, increasing the possibility of using these cells safely for a wide range of applications.

Stem Cells International
 Journal metrics
See full report
Acceptance rate30%
Submission to final decision101 days
Acceptance to publication24 days
CiteScore8.800
Journal Citation Indicator0.820
Impact Factor5.131
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Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. Read the winning articles.