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Conventional human pluripotent stem cells (hPSCs), known for being in a primed state, are pivotal for both basic research and clinical applications since such cells produce various types of differentiated cells. Recent reports on PSCs shed light on the pluripotent hierarchy of stem cells and have promoted the exploration of new stem cell states along with their culture systems. Human naïve PSCs are expected to provide further knowledge of early developmental mechanisms and improvements for differentiation programmes in the regenerative therapy of conventionally primed PSCs. However, practical challenges exist in using naïve-state PSCs such as determining the conditions for hypoxic culture condition and showing limited stable cellular proliferation. Here, we have developed new leukemia inhibitory factor dependent PSCs by applying our previous work, the combination of dibenzazepine and a DOT1L inhibitor to achieve the stable culture of naïve-state PSCs. The potential of these cells to differentiate into all three germ layers was shown both in vitro and in vivo. Such new naïve-state PSCs formed dome-shaped colonies at a faster rate than conventional, primed-state human induced PSCs and could be maintained for an extended period in the absence of hypoxic culture conditions. We also identified relatively high expression levels of naïve cell markers. Thus, non-hypoxia treated, leukemia inhibitory factor-dependent PSCs are anticipated to have characteristics similar to those of naïve-like PSCs, and to enhance the utility value of PSCs. Such naïve PSCs may allow the molecular characterization of previously undefined naïve human PSCs, and to ultimately contribute to the use of human pluripotent stem cells in regenerative medicine and disease modelling.Osteoarthritis (OA) is the most common chronic musculoskeletal disorder. It can affect any joint and is the most frequent single cause of disability in older adults. OA is a progressive degenerative disease involving the entire joint structure in a vicious circle that includes the capsule-bursa tissue inflammation, synovial fluid modifications, cartilage breakdown and erosions, osteochondral inflammatory damage leading to bone erosion and distortion. Research has identified the initial inflammatory-immunologic process that starts this vicious cycle leading to so-called early OA. Research has also identified the role played in the disease advancement by synoviocytes type A and B, chondrocytes, extracellular matrix, local immune-inflammatory mediators and proteases. This article investigates the joint-resident MSCs that play an essential local homeostatic role and regulate cell turn over and tissue repair. Resident MSCs establish and maintain a local regenerative microenvironment. The understanding of OA physiopathology clarifies the core mechanisms by which minimally invasive interventions might be able to halt and reverse the course of early stage OA. Interventions employing PRP, MSCs and exosomes are considered in this article.Wound healing requires well-coordinated events including hemostasis, inflammation, proliferation, and remodeling. Delays in any of these stages leads to chronic wounds, infections, and hypertrophic scarring. Burn wounds are particularly problematic, and may require intervention to ensure timely progression to reduce morbidity and mortality. To accelerate burn wound healing, Platelet-Rich Plasma (PRP)1 can be of value, since platelets release growth factor proteins and inorganic polyphosphates (polyP) that may be integral to wound healing. We used polyP-depleted keratinocyte (HaCaT) and fibroblast cell culture models to determine cell proliferation and scratch-wound repair to determine if polyP, platelet lysate, or combined treatment could accelerate wound healing. While polyP and PRP significantly reduced the open scratch-wound area in fibroblasts and keratinocytes, polyP had no effect on keratinocyte or fibroblast proliferation. PRP was also evaluated as a treatment in a murine model of full thickness wound healing in vivo, including a treatment in which PRP was supplemented with purified polyP. PRP induced significantly more rapid re-epithelialization by Day 3. Pure polyP enhanced the effects of PRP on epithelial tongues, which were significantly elongated in the PRP + high-dose polyP treatment groups compared to PRP alone. Thus, PRP and polyP may serve as an effective therapeutic combination for treating wounds.The main surgical strategy for gastrointestinal tract malignancy is en bloc resection, which consists of not only resection of the involved organs but also simultaneous resection of the surrounding or adjacent mesenteries that contain lymph vessels and nodes. After resection of the diseased organs, the defect of the gastrointestinal conduit is replaced with organs located downstream, such as the stomach and jejunum. learn more However, esophageal and gastric reconstruction using these natural substitutes is associated with a diminished quality of life due to the loss of the reserve function, damage to the antireflux barrier, and dumping syndrome. Thus, replacement of the deficit after resection with the patient's own regenerated tissue to compensate for the lost function and tissue using regenerative medicine will be an ideal treatment. Many researchers have been trying to construct artificial organs through tissue engineering techniques; however, none have yet succeeded in growing a whole organ because of the complicated functions these organs perform, such as the processing and absorption of nutrients. While exciting results have been reported with regard to tissue engineering techniques concerning the upper gastrointestinal tract, such as the esophagus and stomach, most of these achievements have been observed in animal models, and few successful approaches in the clinical setting have been reported for the replacement of mucosal defects. We review the recent progress in regenerative medicine in relation to the upper gastrointestinal tract, such as the esophagus and stomach. We also focus on the functional capacity of regenerated tissue and its role as a culture system to recapitulate the mechanisms underlying infectious disease. With the emergence of technology such as the fabrication of decellularized constructs, organoids and cell sheet medicine, collaboration between gastrointestinal surgery and regenerative medicine is expected to help establish novel therapeutic modalities in the future.

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