The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells. This review discusses the prominent disparities between naïve and primed pluripotency, including signaling pathways, metabolism, and epigenetic status, ultimately facilitating a comprehensive understanding of their significance during early mammalian embryonic development.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Valproic acid (VPA), widely used as an antiepileptic drug, exhibits developmental neurotoxicity when exposure occurs during early or late pregnancy, resulting in various conditions ranging from neural tube defects to autism spectrum disorders. However, toxicity during the very early stages of neural development has not been addressed. Therefore, we investigated the effects of VPA in a model where human pluripotent stem cells differentiate into anterior or posterior neural tissues. Exposure to VPA during the induction of neural stem cells induced different developmental toxic effects in a dose-dependent manner. For instance, VPA induced cell death more profoundly during anteriorly guided neural progenitor induction, while inhibition of cell proliferation and enhanced differentiation were observed during posteriorly guided neural induction. Furthermore, acute exposure to VPA during the posterior induction step also retarded the subsequent neurulation-like tube morphogenesis process in neural organoid culture. These results suggest that VPA exposure during very early embryonic development might exhibit cytotoxicity and subsequently disrupt neural differentiation and morphogenesis processes.

Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don’t alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.

Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Natural killer (NK) cells are gaining growing attention due to their promise for immunotherapy. A fast and accurate system is needed to test NK cell biology and their therapeutic application. Here, we report a lung cancer organoid-based system to evaluate NK cells’ cytotoxicity. We first established the lung cancer organoids on top of Matrigel, which allows the co-culture with NK cells. When co-cultured, NK cells moved close to and inside the lung cancer organoids. When we analyzed by flow cytometry, co-culture of NK cells induced a significantly higher ratio of cell death of lung cancer organoids, suggesting that lung cancer organoids can be employed to test the cytotoxicity of NK cells. Finally, the pre-treatment of NK cells with A83-01, a TGFβ inhibitor, significantly enhanced the cell death of lung cancer organoids by NK cells, indicating that lung cancer organoid-based system faithfully recapitulates cell line-based system in evaluating the in vitro cytotoxicity of NK cells. These data represent that cancer organoid-based NK cell co-culture system is a reliable platform for studying NK cell biology and evaluating their cytotoxicity for screening for NK cell immunotherapy.

The multiple layers of the skin cover and protect our entire body. Among the skin layers, the epidermis is in direct contact with the outer environment and serves as the first line of defense. The epidermis functions as a physical and immunological barrier. To maintain barrier function, the epidermis continually regenerates and repairs itself when injured. Interactions between tissue-resident immune cells and epithelial cells are essential to sustain epidermal regeneration and repair. In this review, we will dissect the crosstalk between epithelial cells and specific immune cell populations located in the epidermis during homeostasis and wound repair. In addition, we will analyze the contribution of dysregulated immune-epithelial interactions in chronic inflammatory diseases.

The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells. This review discusses the prominent disparities between naïve and primed pluripotency, including signaling pathways, metabolism, and epigenetic status, ultimately facilitating a comprehensive understanding of their significance during early mammalian embryonic development.