Publications by authors named "Yo Mabuchi"

Microbiome alterations are reportedly linked to systemic disease progression and medication. However, the effects of central nervous system drugs on the microbiome of patients with neurodegenerative diseases, such as Alzheimer's or Parkinson's disease, are poorly understood. Here, we comprehensively analyzed the effects of medication on the salivary and gut microbiomes of patients with Alzheimer's or Parkinson's disease.

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The direct reprogramming of cells has tremendous potential in in vitro neurological studies. Previous attempts to convert blood cells into induced neurons have presented several challenges, necessitating a less invasive, efficient, rapid, and convenient approach. The current study introduces an optimized method for converting somatic cells into neurons using a nonsurgical approach that employs peripheral blood cells as an alternative source to fibroblasts.

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Background: Salivary microbiome alterations are associated with chronic diseases, such as cardiovascular disease, diabetes, and dementia. These chronic diseases often coexist in older adults, leading to polypharmacy. This situation complicates the relationship between systemic diseases and salivary microbiome dysbiosis.

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Mesenchymal stem/stromal cells (MSCs) are distributed in various tissues and are used in clinical applications as a source of transplanted cells because of their easy harvestability. Although MSCs express numerous cell-surface antigens, single-cell analyses have revealed a highly heterogeneous cell population depending on the original tissue and donor conditions, including age and interindividual differences. This heterogeneity leads to differences in their functions, such as multipotency and immunomodulatory effects, making it challenging to effectively treat targeted diseases.

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Myeloid cells, which originate from hematopoietic stem/progenitor cells (HSPCs), play a crucial role in mitigating infections. This study aimed to explore the impact of mesenchymal stem/stromal cells (MSCs) on the differentiation of HSPCs and progenitors through the C-C motif chemokine CCL2/CCR2 signaling pathway. Murine MSCs, identified as PDGFRαSca-1 cells (PαS cells), were found to secrete CCL2, particularly in response to lipopolysaccharide stimulation.

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Background: Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects.

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Article Synopsis
  • * In this research, the focus was on the CD29+ cell population in bovine muscle, which shows heterogeneity and contains promising subpopulations for cultured meat production.
  • * Specific CD29+ cell types were identified: CD29+CD44-CD344- cells had high adipogenic potential for long-term culture, while CD29+CD44+ cells proliferated quickly but weren't sustainable, enhancing understanding for more effective cultured meat production.
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Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell-cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues.

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Adipose stem and progenitor cells (ASPCs) have been isolated from humans and animals for use in regenerative medicine and therapy. However, knowledge of ASPCs in other species is limited. Particularly, ASPCs in livestock are expected to enhance the fat content and meat composition.

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Although neural stem/progenitor cells derived from human induced pluripotent stem cells (hiPSC-NS/PCs) are expected to be a cell source for cell-based therapy, tumorigenesis of hiPSC-NS/PCs is a potential problem for clinical applications. Therefore, to understand the mechanisms of tumorigenicity in NS/PCs, we clarified the cell populations of NS/PCs. We established single cell-derived NS/PC clones (scNS/PCs) from hiPSC-NS/PCs that generated undesired grafts.

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The incidence of inflammatory bowel diseases (IBD) is increasing worldwide. Mesenchymal stem/stromal cells (MSCs) have immunomodulatory functions and are a promising source for cell transplantation therapy for IBD. However, owing to their heterogeneous nature, their therapeutic efficacy in colitis is controversial and depends on the delivery route and form of transplanted cells.

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Article Synopsis
  • - Schwartz-Jampel syndrome (SJS) is an autosomal recessive disorder caused by mutations in the gene that encodes perlecan, a key basement membrane protein, which leads to symptoms like myotonia—a muscle stiffness condition.
  • - Diagnosing myotonia, especially in neonates and young children, is challenging since it's primarily based on physical examination, and there's limited understanding of how it develops in SJS.
  • - Researchers created a cellular model of SJS using patient-derived stem cells, which showed heightened reactions to acetylcholine, helping to confirm the model's relevance for studying SJS and potentially aiding in the search for effective treatments.
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  • Salivary glands can act as reservoirs for viruses, including SARS-CoV-2, but the infection mechanisms in these glands are not well understood due to a lack of suitable models.
  • Researchers have successfully created human induced salivary glands (hiSGs) from human induced pluripotent stem cells, which can be infected with SARS-CoV-2 and mimic the properties of real salivary glands.
  • The study confirms that these hiSGs can be transplanted into mice and show mature features, making them a valuable tool for studying the role of salivary glands in virus infections and transmission, particularly in asymptomatic individuals.
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  • Hematopoietic stem/progenitor cells (HSCs) rely on interactions with mesenchymal stem/stromal cells (MSCs) to maintain their self-renewal and multipotency, which are crucial for medical applications.
  • Culturing MSCs to increase their numbers leads to a loss of important stem cell traits, including their ability to differentiate and proliferate effectively.
  • The study reveals that the c-Mpl signaling pathway is vital for HSC maintenance and enhances MSC proliferation; without this signaling, both HSC functionality and MSC stem cell markers are diminished.
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  • Myoepithelial (ME) cells in exocrine glands have properties of both epithelial and mesenchymal cells, aiding in fluid secretion through contraction, yet their regulatory mechanisms in salivary glands remain poorly understood.
  • Researchers developed a method using flow cytometry with specific cell surface markers (EpCAM and CD49f) to isolate ME cells and analyze their characteristics, revealing high expression of ME cell markers like alpha-smooth muscle actin (α-SMA).
  • Transcriptome analysis showed that genes related to the epithelial-mesenchymal transition, especially Snai2, were upregulated in ME cells, indicating that the balance between epithelial and mesenchymal traits may be mediated by Snai2 and influenced by Not
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Article Synopsis
  • * MDS cells inhibit the normal functioning of mesenchymal stem cells (MSCs), crucial for supporting blood stem cells, by interfering with their development and bone metabolism.
  • * The study reveals that MDS cells release extracellular vesicles that contribute to this suppression, but this effect can be reversed by promoting MSC differentiation, suggesting potential pathways for treatment.
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Mesenchymal stem cells (MSCs) exhibit self-renewal, multi-lineage differentiation potential and immunomodulatory properties, and are promising candidates for cellular therapy of various tissues. Despite the effective function of MSCs, the gradual loss of stem cell characteristics that occurs with repeated passages may significantly limit their therapeutic potential. A novel 3D shaking method was previously established to generate MSC spheroids in growth medium (GM-spheroids) and successfully maintain the multipotency of expanded MSCs, yet the expression of MSC-related genes was still low.

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Microglial activation followed by recruitment of blood-borne macrophages into the central nervous system (CNS) aggravates neuroinflammation. Specifically, in multiple sclerosis (MS) as well as in experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, activated microglia and macrophages (Mg/Mφ) promote proinflammatory responses and expand demyelination in the CNS. However, a potent therapeutic approach through the systemic route for regulating their functions has not yet been developed.

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Manipulating lymphocyte functions with gene silencing approaches is promising for treating autoimmunity, inflammation, and cancer. Although oligonucleotide therapy has been proven to be successful in treating several conditions, efficient in vivo delivery of oligonucleotide to lymphocyte populations remains a challenge. Here, we demonstrate that intravenous injection of a heteroduplex oligonucleotide (HDO), comprised of an antisense oligonucleotide (ASO) and its complementary RNA conjugated to α-tocopherol, silences lymphocyte endogenous gene expression with higher potency, efficacy, and longer retention time than ASOs.

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The current process of meat production using livestock has significant effects on the global environment, including high emissions of greenhouse gases. In recent years, cultured meat has attracted attention as a way to acquire animal proteins. However, the lack of markers that isolate proliferating cells from bovine tissues and the complex structure of the meat make it difficult to culture meat in a dish.

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Mesenchymal stem/stromal cells (MSCs) are present in various body tissues and help in maintaining homeostasis. The stemness of MSCs has been evaluated . In addition, analyses of cell surface antigens and gene expression patterns have shown that MSCs comprise a heterogeneous population, and the diverse and complex nature of MSCs makes it difficult to identify the specific roles in diseases.

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Junctional adhesion molecules (JAMs) are expressed in diverse types of stem and progenitor cells, but their physiological significance has yet to be established. Here, we report that JAMs exhibit a novel mode of interaction and biological activity in adipose-derived stromal/stem cells (ADSCs). Among the JAM family members, JAM-B and JAM-C were concentrated along the cell membranes of mouse ADSCs.

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Human mesenchymal stem/stromal cells (hMSCs) have garnered enormous interest as a potential resource for cell-based therapies. However, the molecular mechanisms regulating senescence in hMSCs remain unclear. To elucidate these mechanisms, we performed gene expression profiling to compare clonal immature MSCs exhibiting multipotency with less potent MSCs.

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Mesenchymal stromal/stem cells (MSCs), which generally expand into adherent monolayers, readily lose their proliferative and multilineage potential following repeated passages. Floating culture systems can be used to generate MSC spheroids, which are expected to overcome limitations associated with conventional adherent cultures while facilitating scaffold-free cell transplantation. However, the phenotypic characteristics of spheroids after long-term culture are unknown.

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