Stem Cell Reviews and Reports最新文献

Estrogen deficiency-induced uterine atrophy is a major cause of menstrual disorders and infertility in postmenopausal women and patients with premature ovarian failure. However, current hormone replacement therapies carry long-term risks and fail to achieve physiological endometrial regeneration. It has been demonstrated that dimethyloxalylglycine (DMOG) can augment the therapeutic effects of mesenchymal stem cells (MSCs), but the effects of DMOG-pretreated MSCs on Estrogen deficiency-induced uterine atrophy remain unclear. This study aimed to explore whether DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) could repair estrogen deficiency-induced uterine atrophy. The results showed that compared with the MSCs group, the DM group significantly improved the disordered estrous cycle of ovariectomy (OVX) mice, increased serum estradiol (E2) levels, and restored uterine morphology and index, and facilitated the recovery of endometrial thickness and gland number. Masson staining confirmed that the DM group had a more significant reduction in endometrial fibrosis. Immunofluorescence demonstrated enhanced expression of Oct-4 and Nanog in the DM group, which suggests that DMOG-pretreated hUC-MSCs may exert paracrine effects to promote the formation of VSELs, thereby facilitating the remodeling of endometrial epithelial structure. This provides a novel and effective strategy for the treatment of estrogen deficiency-related uterine atrophy.

The effective repair of tendon injuries represents a significant challenge in the selection of an appropriate regeneration strategy. Meanwhile, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been employed in the treatment of a range of diseases due to a number of advantageous characteristics, including low immunogenicity, high proliferation and differentiation potential, extensive availability, ease of large-scale production, absence of ethical constraints, and immunomodulatory functions. It has demonstrated considerable clinical application potential and offer a promising avenue for the treatment of tendon injuries. The core strategies may be broadly classified into three categories: direct stem cell injection, transplantation of biological scaffolds with tissue engineering technology, and the use of stem cell-derived products. This review will provide an in-depth analysis of the pathophysiological mechanisms of tendon repair, describe the unique properties of UC-MSCs, and systematically evaluate the advantages and limitations of these treatment strategies, aiming to provide a solid theoretical basis and scientific guidance for the biological research and clinical application of UC-MSCs in the field of tendon repair. The translational potential of this article: Given the low immunogenicity, good biosafety, and strong differentiation potential possessed by UC-MSCs, it is expected to provide a both safe and effective therapeutic option for tendon injuries through certain processing measures, such as combining UC-MSCs with biomaterials or extracting their products. In addition, the extraction process of UC-MSCs is simple and non-invasive, which makes it easy to realize clinical mass production. Therefore, the use of UC-MSCs for tendon repair is significant for clinical translation of tendon injury treatment.

Background: Despite affecting approximately 30% of the population, the pathogenesis of temporomandibular disorders (TMD) remains poorly understood. Conditions such as disc displacement and joint degeneration are often associated with biomechanical dysfunction. Identifying and categorizing biomarkers in the articular disc may enhance our understanding of disease mechanisms and progression, potentially improving diagnostic accuracy and therapeutic outcomes.

Aim: This review examines patterns among immunohistochemical biomarkers in the articular disc, with a focus on internal derangement and disc displacement. It also explores associations with clinical, radiological, and histological findings, defining the functional and stage-specific relevance of each marker.

Methods: A systematic search of major databases and journals identified studies that used immunohistochemical methods and included control groups. Biomarker patterns were analyzed in isolation and in relation to clinical, radiological, and histological findings. Patient demographics were examined to determine their alignment with disease trends. Study selection followed PRISMA guidelines; bias was assessed using the Newcastle-Ottawa Scale.

Results: The review included 511 patients (579 samples) and 132 controls (158 samples). Analysis identified 24 biomarkers, providing valuable insights into their role in inflammatory progression, ECM remodeling, and tissue degeneration. Biomarkers were classified according to functional and stage-specific patterns, facilitating early detection, refining disease staging, and supporting individualized treatment strategies.

Conclusion: Disc biopsy offers unique insights into the joint- and disc-specific mechanisms that drive TMD progression from disc displacement to degenerative findings. However, its clinical use remains limited by its invasive nature, ethical constraints, and the lack of standardized protocols for reliable study design and validated biomarker profiles.

Human Umbilical Cord-derived Mesenchymal Stromal Cells (hUC-MSCs) represent a promising candidate for regenerative medicine, though their therapeutic potential is constrained by replicative senescence. Pyrroloquinoline quinone (PQQ), a redox-active coenzyme, has been reported to protect against cellular aging. However, its precise role and mechanism of action in mitigating replicative senescence of hUC-MSCs remain to be elucidated. This study employed an integrated approach of phenotypic screening and transcriptomic profiling to systematically evaluate the anti-senescence effects of PQQ on replicatively senescent hUC-MSCs. Our results indicated that PQQ treatment enhanced proliferative capacity, reduced senescence-associated β-galactosidase (SA-β-gal) activity, and attenuated G1 phase cell cycle arrest. Moreover, PQQ improved mitochondrial membrane potential, reduced intracellular reactive oxygen species (ROS) accumulation, and attenuated telomere attrition. RNA sequencing analysis suggests that PQQ treatment appears to alleviate senescence-related transcriptional features, which is consistent with the observed phenotypic improvements. Gene Set Enrichment Analysis (GSEA) revealed a significant upregulation of pathways governing cell cycle progression and DNA replication following PQQ intervention. Key Driver Analysis (KDA) further identified regulators within these pathways, including PLK1, MCM5, and CDC6. Subsequent qPCR validation showed that the expression of these genes, which are critical for DNA replication initiation and mitotic progression, was downregulated in senescent cells and increased following PQQ treatment. In conclusion, the effect of PQQ on the replicative senescence of hUC-MSCs may be related to the upregulation of genes associated with the cell cycle and DNA replication.

Polycomb Repressive Complex 1 (PRC1) is a group of epigenetic regulatory complexes critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent autism spectrum disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available data showed that POGZ highly colocalizes with RING1B and HP1g, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in embryonic mouse cortical cells. Although Pogz knockout (KO) does not compromise stem cell pluripotency, Pogz ablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing bone morphogenetic protein (BMP) signaling. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcription during neuronal differentiation and demonstrate that disrupting this complex impairs BMP signaling, potentially contributing to neurodevelopmental disorders such as ASD.

Metastasis and therapy resistance are main clinical challenges of pancreatic ductal adenocarcinoma (PDAC) still limiting patient`s prognosis. Both are dependent on tumor cell plasticity, which allows rapid adaptation of tumor cells to changing microenvironmental conditions. Epithelial-Mesenchymal-Transition (EMT), a process by which carcinoma cells acquire invasive abilities, is associated with a gain of cancer stem cell (CSC) properties. Different CSC phenotypes were described in PDAC, whereby high levels of the CSC marker Nestin was identified in CSC clones of mesenchymal Panc1 cells, while CSC clones of epithelial Panc89 cells were characterized by a high SOX2 expression. To investigate the functional impact of these CSC markers in PDAC cells with different EMT phenotypes, expression of either CSC marker was silenced in heterogenous (parental) and CSC PDAC populations to analyze their impact on essential malignancy associated properties.SiRNA-mediated knockdown (KD) of NES and/or SOX2 in Panc1 and Panc89 cell variants (parental and CSC population), respectively, was successfully achieved. Decreased NES expression in Panc1 cell variants and decreased SOX2 expression in Panc89 cell variants significantly inhibited self-renewing properties, however, only marginally impacted cell growth, EMT marker expression, migration and invasion properties as well as response to chemotherapy. Overall, our data indicate that Nestin and SOX2 are crucial mediators of self-renewal capabilities of mesenchymal and epithelial PDAC cell variants, respectively, but that further factors are required for the maintenance of other malignancy associated properties.