Cell Biology International最新文献

We previously showed that inhibition of the NF-κB signaling pathway in mesenchymal stromal cells (MSCs) (NKI-MSCs) induces quiescence in co-cultured hematopoietic stem cells (HSCs). This led us to investigate whether NKI-MSCs exert similar growth-inhibitory effects on leukemic cells. We found that both NKI-MSCs and their secretome induce cell cycle arrest in KG1a cells, a cell line of acute myeloid leukemia (AML) origin. Surprisingly, the extracellular vesicles (EVs) isolated from NKI-MSCs supported the proliferation of KG1a cells. This is perhaps the first report showing the opposite effects of MSCs and the EVs secreted by them. Further analysis revealed that microvesicles (MVs) from NKI-MSCs inhibited KG1a cell growth and induced apoptosis, whereas exosomes (Exos) supported proliferation. Our findings could have clinical implications. NKI-MVs, having apoptosis-inducing activity, could serve as an adjunct, off-the-shelf biologic to limit AML growth, enabling reduced-intensity chemotherapy in elderly patients and patients having co-morbidities. NF-κB inhibitors have been tried as chemotherapeutic agents for treating AML patients. However, systemic inhibition of NF-κB may also affect the bone marrow resident MSCs, which in turn could produce EVs supporting the proliferation of AML blasts. Our data could explain the inadequate clinical effectiveness of NF-κB inhibitors in treating AML, and also raise a concern for the systemic use of NF-κB inhibitors in the therapeutic regimen.

Male infertility is a multifactorial condition affecting approximately 8%–12% of reproductive-age couples worldwide, with male factors contributing to nearly half of all cases. Traditional treatments often offer limited efficacy, especially in cases involving testicular toxicity, diabetes-related erectile dysfunction, and aging-associated reproductive decline. In recent years, mesenchymal stem cell-derived exosomes (MSC-EXOS) have emerged as a promising cell-free therapeutic approach due to their ability to carry bioactive molecules—such as proteins, lipids, and microRNAs—that modulate inflammation, oxidative stress, apoptosis, and tissue regeneration. This review highlights the pathophysiology of key male reproductive disorders and explores the therapeutic potential of MSC-EXOS in preclinical models. Evidence demonstrates that exosomes from adipose tissue, bone marrow, and umbilical cord MSCs can improve spermatogenesis, restore hormonal balance, enhance vascular function, and repair damaged testicular architecture. While findings are encouraging, challenges remain regarding optimal delivery, dosage, and translation to clinical settings. This review provides the most comprehensive synthesis of preclinical evidence to date demonstrating that mesenchymal stem cell-derived exosomes consistently outperform traditional MSC therapy across multiple male reproductive disorders while offering superior safety and scalability. These findings establish exosomes as a transformative cell-free platform ready for clinical translation in male infertility, warranting further investigation through clinical trials and mechanistic studies.

Selective migration of tumors to particular organs, referred to as organ tropism, is not arbitrary but guided by intricate molecular interactions and a complex network of various secretory molecules. This site-specific migration is modulated by molecular crosstalk, where cytokines and other effectors help tumor cells adapt to and colonize a new organ by reshaping their epigenetics. It is well established that breast and colorectal cancers, for instance, can epigenetically modify themselves to show a preference for the brain, bones, lungs, and liver but the key modulators are still elusive. Here, we have discussed the key mechanisms, including the critical interacting molecules, cytokines, and pathways that drive this site-specific tropism-based colonization. By synthesizing current knowledge, we highlight central players in this process and discuss their potential as therapeutic targets to inhibit metastasis and improve patient outcomes.

Myxomycetes are remarkable organisms, capable of strikingly complex behaviors and exceptional wound healing, yet the molecular mechanisms underlying their immunity and regenerative capacities remain largely unexplored. In this study, we provide the first evidence that these unique organisms could possess a protein resembling macrophage migration inhibitory factor (MIF). Using a custom MIF polyclonal antibody, we detected signals specifically along the pseudopodia of two myxomycetes species, Physarum polycephalum and Badhamia utricularis. Western blot analysis revealed three distinct bands consistent with potential monomeric, dimeric, and trimeric forms of the protein. Notably, following mechanical injury, this protein accumulated at the sites of damage, suggesting a potential role in injury sensing and tissue repair. In contrast, exposure to GFP-expressing Erwinia carotovora did not alter its localization, indicating that this response is likely independent of non-self-recognition. Although current genomic resources for these myxomycetes do not contain annotated MIF sequences, our findings highlight a previously unrecognized, injury-responsive protein in these organisms. This discovery underscores the sophisticated regenerative capacities of myxomycetes and opens new avenues for exploring immune and repair mechanisms in this ancient and fascinating species.

Epithelial-mesenchymal transition (EMT) and cell migration are two essential cellular processes involved in normal biological events such as embryogenesis, organ development, and wound healing, and are also associated with pathological conditions like cancer metastasis. Recent studies have indicated that the microtubule cytoskeleton and its associated proteins play significant roles in these processes. In this study, we investigated how fidgetin, a microtubule-severing and depolymerizing enzyme, affects EMT and cell migration by depleting it in MDA-MB-231 breast cancer cells. Our data show that depletion of endogenous fidgetin reduces the cell migration rate in both wound-healing and single-cell motility assays. During EMT, transcription factors such as Snail, Slug (Snail2), Twist, and Zeb play pivotal roles by regulating the expression of EMT-related genes. In this study, we found that fidgetin depletion reduces the expression of Slug and Zeb1 in MDA-MB-231 breast cancer cells under both basal and EMT-induced conditions. Consistent with these findings, we observed that fidgetin depletion downregulates N-cadherin and vimentin expression in EMT-induced MDA-MB-231 cells, thereby influencing cell motility. Further investigations revealed that fidgetin also affects microtubule plus-end tracking proteins (+TIPs). Specifically, we detected reduced expression of CLIP-170 in fidgetin-depleted cells. Immunofluorescence analysis showed that EB1 comets occupied a smaller area at microtubule plus ends upon fidgetin depletion. Additionally, the size of focal adhesions was significantly increased, although no changes were observed in the expression levels of focal adhesion kinase (FAK). Our findings indicate that microtubule regulation by fidgetin influences cancer cell motility by altering the expression of EMT-promoting transcription factors and modulating the accumulation of focal adhesion and EB1 proteins. These results suggest that fidgetin could be a promising therapeutic target in cancer.

Thymoquinone (TQ), the major bioactive constituent of Nigella sativa, Asian and African medicinal plant, has attracted growing interest for its anticancer properties. In this study, we investigated the antimetastatic potential of TQ in human colorectal carcinoma (CRC) cell lines SW480 and SW620, representing primary and metastatic stages, respectively. The treatment with several concentration of TQ has significantly reduced cell adhesion to extracellular matrix proteins (fibronectin, collagen I and IV), without affecting adhesion to poly-l-lysine, proving disruption of integrin-mediated attachment. Furthermore, wound healing and transwell migration assays demonstrated that TQ has significantly inhibited CRC cell motility and migratory capacity in a time- and dose-dependent manner. Interestingly, our findings highlight the therapeutic potential of TQ in colorectal cancer by targeting tumor cell dissemination. Thus TQ may represent a promising candidate for the development of novel antimetastatic strategies as a nutraceutical compound in colorectal cancer therapy. Importantly, TQ treatment led to a marked, dose-dependent decrease in MMP9 and MMP2 mRNA expression, as revealed by RT-PCR and densitometric quantification. At the highest doses, MMP9 and MMP2 expression levels were reduced to 0.76- and 0.56-fold (SW480, 30 μM) and to 0.73- and 0.61-fold (SW620, 48 μM) relative to control, respectively. These findings demonstrate that TQ robustly inhibits the transcription of key metastasis-associated markers in CRC cells.

Microglia cells impacted by inflammation and Alzheimer's disease produce toxic reactive oxygen species (ROS), emit signaling molecules, and death as a result of microglia being active due to excessive Ca²⁺ entering the cells. The TRPM2 channel plays a crucial role in Ca²⁺ permeability, inflammation, ROS, and apoptosis changes in the BV2 microglia cells, while glutathione (GSH) treatment reduces the changes through TRPM2 inhibition. However, the effect of TRPM2 inhibitors and GSH treatment on oxidative stress, inflammation, and apoptotic values in BV2 microglia cells activated with LPS and amyloid-beta (Aβ) has not been investigated yet. The study aimed to assess the effects of TRPM2 inhibition and GSH treatment on the values in BV2 cells activated with LPS and Aβ. BV2 cells were divided into five groups: control (CNT), LPS, Aβ, Aβ + LPS, and Aβ + LPS + GSH. Increased levels of inflammation biomarkers (TNF-α, IL-1β, and IL-6), intracellular Ca²⁺ level, cytosolic ROS, mitochondrial membrane dysfunction, cell death, apoptosis, caspases (caspase-3, −8, and −9), and TRPM2 current density were observed in the cells stimulated with LPS and Aβ. These values increased more when LPS and Aβ were incubated together. However, these apoptotic, inflammatory, and oxidant levels decreased in cells treated with GSH and TRPM2 blockers. In conclusion, the involvement of TRPM2 stimulation was demonstrated on Aβ and LPS-induced Ca²⁺ entry, oxidative stress, inflammation, and apoptosis parameters in microglia cells. TRPM2 inhibition by GSH treatment seems to be a potential source for the prevention of Aβ and LPS-induced oxidative stress, apoptosis, and inflammation.

Alterations in driver genes in lung cancer, such as those in EGFR, KRAS, EML4-ALK, and TP53, play pivotal roles in tumor progression, therapeutic response, and resistance development. Therefore, it is important to develop research models that reflect both human tumor characteristics and systemic physiological responses. This review summarizes and compares previous studies of the application and complementarity of organ-chip technologies (including organoids and lung-on-a-chip) and traditional animal models (genetically engineered mouse models and patient-derived xenografts) for investigating the same genetic alterations. Existing literature demonstrates that animal models are well-suited for studying long-term tumor evolution and metastasis because of their intact immune systems, physiological environments, and immune-based therapies. However, organ-chips can rapidly establish models in controllable microenvironments, enabling the high-throughput screening of drugs and analyses of resistance mechanisms. Although both approaches demonstrate consistent trends in oncogenic potential and drug sensitivity across multiple genetic alterations, they differ in terms of time efficiency, microenvironmental control, and the capacity to recapitulate systemic responses. Thus, the two platforms may be complementary in preclinical lung cancer research, and their combined application may enhance the accuracy of gene function validation, drug efficacy evaluation, and clinical translation.

The rising prevalence of retinal diseases underscores the need for personalized neuroprotection strategies. Mesenchymal stem cells (MSCs) exhibit paracrine neuroprotective potential and are used clinically when transplantation is unnecessary. This study evaluated MSC-mediated photoreceptor rescue and its enhancement using clinically relevant drugs; nicotinamide (NIC), vasoactive intestinal peptide (VIP), retinoic acid (ATRA), or their combination. Optimizing and personalizing treatments in accordance to retinal damage severity maximizes photoreceptor rescue, offering a targeted approach to retinal disease management. Adipose-derived MSCs were cocultured with spontaneously degenerating neuroretina explants for 6 days. VIP (5 µM), NIC (10 mM), and ATRA (5 µM) were applied individually and in combination. Photoreceptor recovery and structural changes in the inner limiting membrane (ILM), outer nuclear layer (ONL), and inner nuclear layer (INL) were assessed using Toluidine, Rhodopsin immunofluorescence, and DAPI staining. MSCs alone improved photoreceptor, ILM, ONL, and INL recovery compared to the control. However, combining VIP, NIC, and ATRA led to greater improvement, with NIC being the most effective single treatment. The combination of VIP and NIC preserved retinal structure better than VIP, NIC, and ATRA together, although none fully restored the original structure. Personalized treatment approaches, combining MSCs with specific drugs, can significantly enhance retinal neuroprotection tailored to the degree of damage, emphasizing the need for individualized strategies in retinal disease management.