NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.

Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (known as SCN1A and NaV1.1, respectively); however, the functions of NaV1.1 are unclear.

Potential role of stem cells from human exfoliated deciduous teeth in inducing liver regeneration.

Background And Aim: Even with advancement of medical technologies, liver transplantation still faces several major challenges. Hence, other treatment modalities are urgently needed for patients with end-stage liver disease. Stem cells from human exfoliated deciduous teeth (SHED) was discovered to have highly proliferative and pluripotent properties; including differentiation into hepatocyte-like cells.

TRPV4-mediated Ca deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons.

Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca permeable nonselective cation channel, cause TRPV4-related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4-mediated Ca deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain-of-function TRPV4 mutation, c.

Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca regulation in autism spectrum disorder.

Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology.

Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders.

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management.

Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment.

Systemic transplantation of mesenchymal stem cells (MSCs), such as bone marrow MSCs (BMMSCs) and stem cells from human exfoliated deciduous teeth (SHED), is considered a prominent treatment for osteopenia. However, the mechanism of action of the transplanted MSCs has been poorly elucidated. In the recipient target tissue, including bone and bone marrow, only a few donor MSCs can be detected, suggesting that the direct contribution of donor MSCs may not be expected for osteopenia treatment.

Nupr1 deficiency downregulates HtrA1, enhances SMAD1 signaling, and suppresses age-related bone loss in male mice.

Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-β signaling was markedly downregulated in Nupr1-KO osteocytes.

Targeting hepatic oxidative stress rescues bone loss in liver fibrosis.

Objective: Chronic liver diseases often involve metabolic damage to the skeletal system. The underlying mechanism of bone loss in chronic liver diseases remains unclear, and appropriate therapeutic options, except for orthotopic liver transplantation, have proved insufficient for these patients. This study aimed to investigate the efficacy and mechanism of transplantation of immature hepatocyte-like cells converted from stem cells from human exfoliated deciduous teeth (SHED-Heps) in bone loss of chronic liver fibrosis.

Dopamine-related oxidative stress and mitochondrial dysfunction in dopaminergic neurons differentiated from deciduous teeth-derived stem cells of children with Down syndrome.

Down syndrome (DS) is one of the common genetic disorders caused by the trisomy of human chromosome 21 (HSA21). Mitochondrial dysfunction and redox imbalance play important roles in DS pathology, and altered dopaminergic regulation has been demonstrated in the brain of individuals with DS. However, the pathological association of these elements is not yet fully understood.

Protocol to generate xenogeneic-free/serum-free human dental pulp stem cells.

Human dental pulp stem cell (hDPSCs)-based therapy is a feasible option for regenerative medicine, such as dental pulp regeneration. Here, we show the steps needed to colony-forming unit-fibroblasts (CFU-F)-based isolation, expansion, and cryopreservation of hDPSCs for manufacturing clinical-grade products under a xenogeneic-free/serum-free condition. We also demonstrate the characterization of hDPSCs by CFU-F, flow cytometric, and multipotent assays.

Sevoflurane concentration for cannulation in developmental disabilities.

Objective: The goal of this study was to compare the end-tidal sevoflurane concentration and time for intravenous cannulation at induction of anesthesia using sevoflurane with or without nitrous oxide in healthy children and in those with developmental disabilities.

Methods: Normal and developmentally disabled children were anesthetized by inhalation of sevoflurane with nitrous oxide or with nitrous oxide-free oxygen, and intravenous cannulae were introduced. Nitrous oxide was stopped after loss of consciousness.

Dental pulp stem cells as a therapy for congenital entero-neuropathy.

Hirschsprung's disease is a congenital entero-neuropathy that causes chronic constipation and intestinal obstruction. New treatments for entero-neuropathy are needed because current surgical strategies have limitations5. Entero-neuropathy results from enteric nervous system dysfunction due to incomplete colonization of the distal intestine by neural crest-derived cells.

A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus.

Recent advances in mesenchymal stem/stromal cell (MSC) research have led us to consider the feasibility of MSC-based therapy for various diseases. Human dental pulp-derived MSCs (hDPSCs) have been identified in the dental pulp tissue of deciduous and permanent teeth, and they exhibit properties with self-renewal and in vitro multipotency. Interestingly, hDPSCs exhibit superior immunosuppressive functions toward immune cells, especially T lymphocytes, both in vitro and in vivo.

Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency.

Background: Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent.

Methods: To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED.

Targeting of Deciduous Tooth Pulp Stem Cell-Derived Extracellular Vesicles on Telomerase-Mediated Stem Cell Niche and Immune Regulation in Systemic Lupus Erythematosus.

Systemic transplantation of stem cells from human exfoliated deciduous teeth (SHED) is used to treat systemic lupus erythematosus (SLE)-like disorders in MRL/ mice. However, the mechanisms underlying the SHED-based therapy remain unclear. In this study, we hypothesized that trophic factors within SHED-releasing extracellular vesicles (SHED-EVs) ameliorate the SLE-like phenotypes in MRL/ mice.

Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells.

Background: Stem cells from human exfoliated deciduous teeth (SHED) have been reported to show the in vivo and in vitro hepatic differentiation, SHED-Heps; however, the cholangiogenic potency of SHED-Heps remains unclear. Here, we hypothesized that SHED-Heps contribute to the regeneration of intrahepatic bile duct system in chronic fibrotic liver.

Methods: SHED were induced into SHED-Heps under cytokine stimulation.

Phosphorylation-dependent osterix degradation negatively regulates osteoblast differentiation.

Proteasome inhibitors exert an anabolic effect on bone formation with elevated levels of osteoblast markers. These findings suggest the important role of the proteasomal degradation of osteogenic regulators, while the underlying molecular mechanisms are not fully understood. Here, we report that the proteasome inhibitors bortezomib and ixazomib markedly increased protein levels of the osteoblastic key transcription factor osterix/Sp7 (Osx).

A model study for the manufacture and validation of clinical-grade deciduous dental pulp stem cells for chronic liver fibrosis treatment.

Background: Human deciduous pulp stem cells (hDPSCs) have remarkable stem cell potency associated with cell proliferation, mesenchymal multipotency, and immunosuppressive function and have shown beneficial effects in a variety of animal disease models. Recent studies demonstrated that hDPSCs exhibited in vivo anti-fibrotic and anti-inflammatory action and in vivo hepatogenic-associated liver regeneration, suggesting that hDPSCs may offer a promising source with great clinical demand for treating liver diseases. However, how to manufacture ex vivo large-scale clinical-grade hDPSCs with the appropriate quality, safety, and preclinical efficacy assurances remains unclear.

Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla.

Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs]) are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA) on odontogenic differentiation of SCAPs in vitro and in vivo.

Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA.

Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson's disease.

Wilson's disease (WD) is an inherited metabolic disease arising from ATPase copper transporting beta gene (ATP7B) mutation. Orthotoropic liver transplantation is the only radical treatment of fulminant WD, although appropriate donors are lacking at the onset of emergency. Given the hepatogenic capacity and tissue-integration/reconstruction ability in the liver of stem cells from human exfoliated deciduous teeth (SHED), SHED have been proposed as a source for curing liver diseases.

Suppression of AKT-mTOR signal pathway enhances osteogenic/dentinogenic capacity of stem cells from apical papilla.

Background: Stem cells from apical papilla (SCAP) are a subpopulation of mesenchymal stem cells (MSCs) isolated from the apical papilla of the developing tooth root apex of human teeth. Because of their osteogenic/dentinogenic capacity, SCAP are considered as a source for bone and dentin regeneration. However, little is understood about the molecular mechanism of osteogenic/dentinogenic differentiation of SCAP.

Pamidronate decreases bilirubin-impaired cell death and improves dentinogenic dysfunction of stem cells from human deciduous teeth.

Background: Hyperbilirubinemia that occurs in pediatric liver diseases such as biliary atresia can result in the development of not only jaundice in the brain, eyes, and skin, but also tooth abnormalities including green pigmentation and dentin hypoplasia in the developing teeth. However, hyperbilirubinemia-induced tooth impairments remain after liver transplantation. No effective dental management to prevent hyperbilirubinemia-induced tooth impairments has been established.

Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells.

Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs).

Bilirubin reversibly affects cell death and odontogenic capacity in stem cells from human exfoliated deciduous teeth.

Objective: Hyperbilirubinemia in patients with biliary atresia causes deciduous tooth injuries such as green pigmentation and dentin hypoplasia. In patients with biliary atresia who received liver transplantation, tooth structure appears to be recovered radiographically. Nevertheless, little is known about cellular mechanisms underlying bilirubin-induced damage and suppression of deciduous tooth formation.