Stem Cell Reviews and Reports最新文献

Cancer Stem Cells (CSCs) represent a heterogeneous group of tumor cells that possess the innate ability to self-renew and differentiate, which also contributes to their resistance to first-line therapies. What sets CSCs apart from others is their crucial role in the recurrence of cancer, metastasis, and varied clinical responses against anti-cancer drugs, which makes them challenging to target. In recent years, there has been growing evidence that therapies capable of eliminating CSC niches or specifically targeting their core survival mechanisms are a potential means of providing a sustainable, long-term response to therapy and increasing disease-free survival rates. Bioactive compounds from natural sources have gained immense interest for their bio-efficacy, low toxicity profiles, and wide therapeutic index (TI), especially with their broad-spectrum ability of targeting multiple pathways while having little or no systemic side effects. Bioactive compounds can target major signaling pathways (Wnt/β-catenin, Notch, Hippo-YAP/TAZ, Hedgehog, PI3K/Akt/mTOR, NF-κB) to induce apoptosis, inhibit epithelial-mesenchymal transition (EMT), disrupt cancer stem cell niches, and other effects that suggest they resensitize to chemotherapeutic agents. Plant-derived biologics may be used as unique strategies targeting CSCs or as adjuncts reconstituted with custom conventional treatment plans, to mitigate drug resistance with mechanisms that involve targeting CSC metabolism, blocking protective autophagy, and the epigenetic landscape. The use of nanotechnology for targeted delivery of bioactive compounds is anticipated to provide better stability, bioavailability, and tumor accumulation. In this review, we outline a range of approaches using bioactive compounds for the eradication of CSCs, focusing on the mechanisms by which they work, the preclinical and clinical evidence supporting them, and their role in combination therapy approaches. This review also gives a comprehensive understanding of various other strategies and latest advancements that do not directly target the CSCs, including differentiation therapy, metabolic targeting, and immunomodulation, which, when used in conjunction with bioactive compounds, may resensitize the drug-resistant CSC population. We also discuss the therapeutic and translational potential of bioactive compounds and the future possibilities of combination, multi-targeted, CSC-based treatment strategies to eliminate tumor recurrences and improve cancer outcomes for patients.

Despite recent novel drug approvals and numerous treatment options, the steroid-refractory chronic graft-versus-host disease (SR-cGvHD) remains a significant clinical problem. We aimed to evaluate the efficacy and safety of available therapies in adult patients, based on a systematic review and meta-analysis. The analyzed treatment options included: axatilimab, belumosudil, extracorporeal photopheresis (ECP), ibrutinib, imatinib, rovadicitinib, and ruxolitinib. The endpoints included: best overall response rate (ORR), 12-month failure-free survival (FFS), the ratio of patients who discontinued therapy due to unacceptable toxicity, and the ratio of patients who experienced grade 3-5 adverse events. Rovadicitinib was the most effective treatment option, with manageable safety profile. Axatilimab produced a high response rate, yet worse 12-month FFS. It was a very safe option in SR-cGvHD. Despite promising efficacy, belumosudil produced the highest incidence of adverse events of all drugs. Ruxolitinib was proven to be an efficient and safe drug. Ibrutinib produced poor results in terms of both efficacy and safety. ECP was proven to be a very safe therapy, without spectacular efficacy. The analysis of imatinib yielded inconsistent results. As cGvHD is a disease with a heterogeneous clinical image, clinical experience remains an important factor that affects treatment choice for patients with certain disease manifestations.

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.

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.

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.

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.