Galectin-3 Plays an Important Role in BMP7-Induced Cementoblastic Differentiation of Human Periodontal Ligament Cells by Interacting with Extracellular ComponentsRead the full article
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.
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.
Latest ArticlesMore articles
Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm
Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.
METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation
Mesenchymal stem cells (MSCs) have been considered a potential method for the regeneration of tooth and maxillofacial bone defects based on the multidirectional differentiation characteristics of MSCs. miRNAs have been found to play a key role in the differentiation of MSCs. However, its effectiveness still needs to be improved, and its internal mechanism is still unclear. In the present study, our data discovered that the knockdown of miR-196b-5p promoted alkaline phosphatase (ALP) activity assay, mineralization in vitro, and expressions of osteo/odontogenic differentiation markers DSPP and OCN and enhanced in vivo osteo/odontogenic differentiation of stem cells of the apical papilla (SCAPs). Mechanistically, the results indicated that METTL3-dependent N6-methyladenosine (m6A) methylation inhibited miR-196b-5p maturation by the microprocessor protein DGCR8. Moreover, miR-196b-5p indirectly negatively regulates METTL3 in SCAPs. Then, METTL3 was found to strengthen the ALP activity assay, mineralization, and expressions of osteo/dentinogenic differentiation markers. Taken together, our findings highlight the critical roles of the METTL3-miR-196b-5p signaling axis in an m6A-dependent manner in osteo/odontogenic differentiation of SCAPs, identifying some potential targets for tooth and maxillofacial bone defects.
MAGEB2-Mediated Degradation of EGR1 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cell Lines
Spermatogonial stem cells are committed to initiating and maintaining male spermatogenesis, which is the foundation of male fertility. Understanding the mechanisms underlying SSC fate decisions is critical for controlling spermatogenesis and male fertility. However, the key molecules and mechanisms responsible for regulating human SSC development are not clearly understood. Here, we analyzed normal human testis single-cell sequencing data from the GEO dataset (GSE149512 and GSE112013). Melanoma antigen gene B2 (MAGEB2) was found to be predominantly expressed in human SSCs and further validated by immunohistology. Overexpression of MAGEB2 in SSC lines severely weakened cell proliferation and promoted apoptosis. Further, using protein interaction prediction, molecular docking, and immunoprecipitation, we found that MAGEB2 interacted with early growth response protein 1 (EGR1) in SSC lines. Reexpression of EGR1 in MAGEB2 overexpression cells partially rescued decreased cell proliferation. Furthermore, MAGEB2 was shown to be downregulated in specific NOA patients, implying that abnormal expression of MAGEB2 may impair spermatogenesis and male fertility. Our results offer new insights into the functional and regulatory mechanisms in MAGEB2-mediated human SSC line proliferation and apoptosis.
SETD4 Confers Cancer Stem Cell Chemoresistance in Nonsmall Cell Lung Cancer Patients via the Epigenetic Regulation of Cellular Quiescence
Increasing evidence indicates that quiescent cancer stem cells (CSCs) are a root cause of chemoresistance. SET domain-containing protein 4 (SETD4) epigenetically regulates cell quiescence in breast cancer stem cells (BCSCs), and SETD4-positive BCSCs are chemoradioresistant. However, the role of SETD4 in chemoresistance, tumor progression, and prognosis in nonsmall cell lung cancer (NSCLC) patients is unclear. Here, SETD4-positive cells were identified as quiescent lung cancer stem cells (qLCSCs) since they expressed high levels of ALDH1 and CD133 and low levels of Ki67. SETD4 expression was significantly higher in advanced-stage NSCLC tissues than in early-stage NSCLC tissues and significantly higher in samples from the chemoresistant group than in those from the chemosensitive group. Patients with high SETD4 expression had shorter progression-free survival (PFS) times than those with low SETD4 expression. SETD4 facilitated heterochromatin formation via H4K20me3, thereby leading to cell quiescence. RNA-seq analysis showed upregulation of genes involved in cell proliferation, glucose metabolism, and PI3K-AKT signaling in activated qLCSCs (A-qLCSCs) compared with qLCSCs. In addition, SETD4 overexpression facilitated PTEN-mediated inhibition of the PI3K-mTOR pathway. In summary, SETD4 confers chemoresistance, tumor progression, and a poor prognosis by regulating CSCs in NSCLC patients.
Exosomal miR-141-3p from PDLSCs Alleviates High Glucose-Induced Senescence of PDLSCs by Activating the KEAP1-NRF2 Signaling Pathway
Human periodontal ligament stem cells (PDLSCs) are the most promising stem cells for periodontal tissue engineering. Senescent PDLSCs have diminished abilities to proliferate and differentiate, affecting the efficiency of periodontal tissue repair and regeneration. Stem cell-derived exosomes are important participants in intercellular information exchange and can help ameliorate senescence. In this study, we investigated PDLSC senescence in a high glucose microenvironment as well as the ability of human periodontal ligament stem cell-derived exosomes (PDLSC-Exos) to alleviate cellular senescence and the underlying mechanisms. Herein, PDLSCs and PDLSC-Exos were isolated and extracted. Then, cellular senescence indicators were evaluated after high glucose (25 mM) treatment of cultured PDLSCs. PDLSC-Exos were cocultured with senescent PDLSCs to further explore the role of PDLSC-Exos in cellular senescence and determine the differences in cellular oxidative stress levels after PDLSC-Exo treatment. Next, we investigated whether PDLSC-Exos alleviated cellular senescence by restoring the balance of oxidative stress signals and explored the underlying molecular pathways. We discovered that PDLSCs underwent premature senescence due to high glucose culture, but they were rejuvenated by PDLSC-Exos. The rejuvenating effects of PDLSC-Exos were notably reversed by cotreatment with ML385, an inhibitor of nuclear factor erythroid 2-related factor 2 (NRF2), indicating that this recovery depended on NRF2 activation. Further analyses revealed that microRNA-141-3p (miR-141-3p) was expressed at relatively high levels in PDLSC-Exos and was instrumental in PDLSC-Exo-mediated restoration by downregulating Kelch-like ECH-associated protein 1 (KEAP1), which is a negative regulator of NRF2 expression. Our findings suggest that PDLSC-Exos alleviate high glucose-induced senescence of PDLSCs by transferring miR-141-3p to activate the KEAP1-NRF2 signaling pathway. Based on this research, PDLSC-Exos may behave similarly to their parental PDLSCs and have significant effects on cellular senescence by delivering their encapsulated bioactive chemicals to target cells.
Bone Marrow-Derived Mesenchymal Stem Cells and γ-Secretase Inhibitor Treatments Suppress Amyloid-β25–35-Induced Cognitive Impairment in Rat Dams and Cortical Degeneration in Offspring
Alzheimer’s disease (AD) is the most frequent cause of age-related neurodegeneration and ensuing cognitive impairment. Progressive deposition of extracellular amyloid beta (Aβ) aggregates (plaques) and intracellular hyperphosphorylated Tau protein (p-Tau) are the core pathological markers of AD but may precede clinical symptoms by many years, presenting a therapeutic window of opportunity. Females are more frequently afflicted by AD than males, necessitating evaluation of novel treatments for the female population. The current study examined the protective efficacies of intravenous bone marrow-derived mesenchymal stem cells (BM-MSCs) and oral gamma-secretase inhibitor-953 (GSI-953) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring induced by intracerebroventricular injection of Aβ25–35 prior to pregnancy. The Aβ25–35 (AD) group exhibited significant () impairments in the Y-maze and novel object recognition test performance prior to conception. Histological analysis of the offspring cortex revealed substantial dendritic shrinkage and activation of microglial cells, while neurochemical analysis demonstrated significant increases in the proinflammatory cytokine interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In contrast, BM-MSC or GSI-953 treatment of dams following Aβ25–35 injection significantly () reduced the number and size of activated microglial cells, markedly increased dendrite length, and reversed proinflammatory cytokine elevations in offspring. Moreover, BM-MSC or GSI-953 treatment reversed the Aβ25–35-induced amyloid precursor protein and p-Tau elevations in the offspring brain; these changes were accompanied by upregulation of the brain-derived neurotrophic factor and downregulation of glycogen synthase kinase-3β in the serum and brain. Treatment with BM-MSCs or GSI-953 also reversed Aβ25–35-induced elevations in different gene expressions in the neonatal cortex. Finally, treatment of dams with BM-MSCs or GSI-953 prevented the Aβ25–35-induced disruption of newborn brain development. Thus, BM-MSC and GSI-953 treatments have broad-spectrum effects against Aβ25–35-induced brain pathology, including the suppression of neural inflammation, restoration of developmental plasticity, and promotion of neurotrophic signaling.