Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into all three germ layers. However, the primary regulators of hPSC cell cycle dynamics remain unclear. To identify novel regulators of hPSC proliferation, transcriptomic profiling of undifferentiated hPSCs and somatic cells was performed via next-generation sequencing. Stomatin-like protein 2 (STOML2) and prohibitin (PHB) were among the upregulated genes in hPSCs and were closely associated with the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. Temporal expression analysis indicated that STOML2 and PHB decreased during differentiation and increased during reprogramming. Short hairpin RNA (shRNA)-mediated knockdown of STOML2 in hPSCs caused phenotypic changes. Gene expression analyses demonstrated reduced OCT4, NANOG, PHB, and phosphorylated ERK, alongside increased differentiation markers across all three germ layers. The STOML2-PHB axis is essential for maintaining hPSC identity by sustaining ERK/MAPK activity and cell cycle structure. This study identified STOML2 as a key pluripotency regulator and provides new insight into intrinsic stem cell fate control.

Ovarian cancer remains one of the most lethal gynecologic malignancies, with limited responsiveness to standard chemotherapy and poor long-term prognosis. Tumor-associated macrophages, particularly M2-polarized populations, play a crucial role in immune suppression and tumor progression. Human induced pluripotent stem cells (hiPSCs) can differentiate into functional immune cells, providing an unlimited and patient-specific source for cell-based immunotherapy. In this study, we investigated the therapeutic potential of hiPSC-derived macrophages (hiMACs), specifically M1-polarized hiMACs, against ovarian cancer. In a co-culture system, M1-hiMACs significantly reduced the viability of ovarian cancer cells, inducing apoptosis and necrosis, whereas M0 macrophages showed minimal effects. In vivo, intravenous administration of M1-hiMACs into nude mice bearing ovarian cancer cells resulted in a dose-dependent reduction in tumor volume. Furthermore, combination therapy with paclitaxel and M1-hiMACs led to greater tumor regression and enhanced histological necrosis compared to either treatment alone. These findings demonstrate the potent anti-tumor effects of M1-hiMACs and highlight their potential for cellular immunotherapy for ovarian cancer, particularly in combination with chemotherapy.

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight in vitro. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress in vitro. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation. Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.

Transcription factor CP2-like protein 1 (Tfcp2l1), a naïve pluripotency transcription factor, is expressed in both early embryonic and adult tissues, where it enforces pluripotency of embryonic stem cells (ESCs) and stemness features of cancer cells, respectively. However, the detailed molecular pathways by which Tfcp2l1 is regulated in early embryonic development and cancer cells remain unknown. Here, we identified the pseudophosphatase dual specificity phosphatase 27 (Dusp27), also known as serine/threonine/tyrosine-interacting like-2, as a novel Tfcp2l1-interacting protein through a sterile alpha motif-like domain in the C-terminus of Tfcp2l1 in murine ESCs. The interaction between Dusp27 and Tfcp2l1 was dependent on the cell cycle status and increased during mitosis. Expression of Dusp27 was upregulated during naïve pluripotency and repressed during spontaneous differentiation of murine ESCs. Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

Mitigating obesity is a pivotal strategy for addressing metabolic diseases, including cardiovascular diseases, liver diseases, and diabetes. Although pear extract exhibits various pharmacological effects in regenerative diseases, such as skin, nerve, and adipose tissue dysfunction, by eliminating excessive reactive oxygen species, its exact clinical role in obesity has not been well studied. In this study, we investigated the efficacy and safety of pear extract (UPhenon®), a dietary ingredient extracted from unripe pear (Pyrus pyrifolia), in Korean participants with obesity. The participants underwent a 12-week, randomized, double-blind placebo-controlled trial. Body fat mass, body weight, body mass index (BMI), and hematological and blood chemistry parameters were assessed. No adverse effects or significant changes were observed in the supplementation or placebo groups. Additionally, the two groups did not differ significantly in body fat mass, body weight, BMI, hematological parameters, or blood chemistry parameters, except for the liver-specific enzyme, aspartate aminotransferase. Interestingly, compared with the supplementation and placebo groups, after 12 weeks of pear extract administration, a significant decrease in aspartate aminotransferase levels was recorded, indicating that pear extract partially attenuates obesity-induced liver damage. Furthermore, when compared with baseline measurements, a significant reduction in body fat mass (-802.61±1,460.82 g, p<0.0007), body weight (-1.28±1.29 kg, p<0.0001), and BMI (-0.46±0.46 kg/m2, p<0.0001) was observed after 12 weeks of pear extract administration. Taken together, our results suggest that pear extract supplementation may effectively reduce obesity without adverse effects and it may be a promising alternative to synthetic anti-obesity drugs.

Nanog is a key transcription factor that regulates the self-renewal and pluripotency of embryonic stem cells (ESCs). Although Kap1 has been demonstrated to regulate the stability of stemness factors, including Oct4 and Lin28A, its role in regulating Nanog protein stability in ESCs remains unexplored. In the present study, we examined the interaction between Kap1 and Nanog and its role in stabilizing the Nanog protein. Immunoprecipitation assays revealed that Nanog specifically interacted with the coiled-coil domain of Kap1. Kap1 overexpression increased the stability of the Nanog protein by inhibiting its ubiquitination and proteasomal degradation, whereas Kap1 silencing accelerated Nanog degradation. Furthermore, Kap1 overexpression inhibits Nanog degradation by interfering with the binding of Nanog to Fbxw8, an E3 ubiquitin ligase that promotes Nanog degradation via a proteasome-dependent process. These results indicate that Kap1 acts as a key regulator to preserve ESC properties by modulating the protein stability of stemness factors, including Oct4, Lin28A, and Nanog.

Brain organoids have emerged as transformative models for studying human neurodevelopment, neurological disorders, and personalized therapeutics. Central to their utility is the ability to monitor neural activity with high spatial and temporal resolution. Traditional electrophysiological tools-such as planar microelectrode arrays and patch-clamp techniques-offer limited access to the three-dimensional and dynamic nature of organoid neural networks. Recent technological advancements have led to the development of next-generation platforms including surface-embedded, flexible, and fully implantable electrodes. Moreover, multifunctional probes incorporating optical, chemical, and mechanical sensing open new avenues for multimodal interrogation of organoid physiology. This review summarizes the current state of electrophysiological technologies applied to brain organoids, highlighting innovations in recording fidelity, spatiotemporal resolution, and device-tissue integration. We also discuss key challenges such as maintaining organoid viability, achieving sufficient electrode density, and enabling non-disruptive, chronic interfacing throughout organoid development. Looking forward, future systems are expected to evolve toward ultra-dense, multimodal, and closed-loop interfaces capable of investigating organoid function throughout extended growth periods. These advances will not only deepen our understanding of brain-like activity in organoids but also support the design of more functionally accurate and translationally relevant neural models.

Endometrial stem cells (EnSCs) are mesenchymal stem cells (MSCs) derived from endometrial tissue and serve as a valuable MSC source, as they are naturally replenished during menstruation. Exosomes, vesicles secreted by cells, contain various biomolecules such as proteins and nucleic acids and play crucial roles in intracellular communication, protein and nucleic acid metabolism, immune response regulation, and antigen presentation. This study investigated the protein profiles of EnSC-derived exosomes isolated from the endometrium of menstruating women and compared them with those of adipose-derived stem cell (ASC)-derived exosomes. After isolating EnSCs and ASCs, MSC characteristics were confirmed, and the purified exosomes were analyzed to determine their individual protein compositions. EnSCs, which can be obtained through non-invasive methods, exhibit multipotency similar to other MSCs and demonstrate rapid proliferation in vitro. Proteomic analysis of exosomal proteins revealed that 236 proteins were significantly more abundant in EnSC-derived exosomes than in ASC-derived exosomes, whereas 84 proteins were significantly more abundant in ASC-derived exosomes than in EnSC-derived exosomes. These findings indicate that EnSC-derived exosomes contain unique proteins compared to ASC-derived exosomes, as demonstrated through proteomic profiling. While further clinical studies are required, EnSCs hold promise as a potential therapeutic option in regenerative medicine, similar to current cell therapy products under development.

Human pluripotent stem cell (hPSC)-derived brain organoids have emerged as innovative models for drug screening and cytotoxicity evaluation. However, their inherent cellular heterogeneity presents challenges in isolating targeted neuronal populations, such as upper motor neurons, which are crucial for motor cortex function. In this study, we developed motor cortex-like organoids enriched with excitatory glutamatergic and inhibitory GABAergic neurons to assess neurotoxicity in the upper motor neurons–a key component of voluntary motor control. By optimizing the differentiation protocols, we achieved robust expression of vGlut1 in excitatory neurons and GABA in inhibitory neurons by day 30 of the differentiation. The organoids were generated by co-culturing progenitor cells during the early differentiation phase, followed by lineage-specific maturation. Comparative analyses demonstrated that these organoids more accurately recapitulate the human cortical architecture than traditional neural cell line (SK-N-SH neuroblastoma cells). We observed that measures of cell viability and integrity—assessed via cleaved caspase-3 levels, growth-associated protein 43 (GAP43), and autophagy-related protein 5 (ATG5)—were significantly higher in 3D organoid cultures compared to conventional 2D systems. In toxicological assays, the motor cortex-like organoids exhibited a dose-dependent response to both toxic and non-toxic compounds, highlighting their potential as high-fidelity neurotoxicity screening models. Our findings suggest that hPSC-derived motor cortex-like organoids serve as a robust, physiologically relevant model that can replace animal models in toxicity assessments, offering enhanced accuracy in evaluating compounds that impact the motor cortex while reflecting better human brain physiology.

Compared with conventional mesenchymal stem cells (MSCs), induced mesenchymal stem cells (iMSCs) from induced pluripotent stem cells are unique cell sources for tissue regeneration. The effect of extracellular vesicles (EVs) secreted from iMSCs on inhibiting acute kidney injury (AKI) to chronic kidney disease (CKD) transition was not reported. In this study, we investigated whether EVs from iMSCs (iMSC-EVs) could inhibit AKI-to-CKD transition. iMSC-EVs exhibited the general characteristics of EVs, such as protein marker expression, morphology, and size. Additionally, iMSC-EVs were detected in renal tissues after intravenous injection. In human renal tubular epithelial cells, the increase in pro-fibrotic gene expression in response to transforming growth factor β1 treatment was decreased by iMSC-EVs. In a mouse model of the AKI-to-CKD transtion induced by folic acid, repeated administration of iMSC-EVs restored renal function at day 14. Specifically, iMSC-EVs reduced interstitial fibrosis, sustained inflammation, various types of cell death, and the number of immune cells infiltrating kidneys. Capillary rarefaction in renal tissue was also reversed by iMSC-EVs. Our results demonstrate that iMSC-EVs reduced interstitial fibrosis, inflammation, and cell death occurring during the CKD transition after AKI. Thus, iMSC-EVs have the potential to block AKI-to-CKD transition.