Stem Cell Res Ther
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In the context of regenerative medicine and cellular therapies, the treatment under study often targets a less common disease or condition for which recruitment of a large number of research participants at any given site is challenging, if not impossible. One way to overcome this challenge is with a multi-centre clinical trial. ⋯ Second, it considers the regulatory limitations and barriers surrounding the initiation of such trials in Canada, the USA and Europe. Third, it concludes with a set of recommendations for facilitating multi-centre clinical trials, at both national and international levels.
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During the last decade, mesenchymal stem cells (MSCs) have gained much attention in the field of regenerative medicine due to their capacity to differentiate into different cell types and to promote immunosuppressive effects. However, the underlying mechanism of MSC-mediated immunoregulation is not fully understood so far. Macrophages are distinguished in classical activated, pro-inflammatory M1 and alternatively activated M2 cells, which possess different functions and transcriptional profiles with respect to inflammatory responses. As polarization is not fixed, macrophage functional plasticity might be modulated by the microenvironment allowing them to rapidly react to danger signals and maintaining tissue homeostasis. ⋯ Preconditioning of MSCs highly strengthens their capacity to regulate macrophage features and to promote immunosuppression. Repression of M1 polarization during inflammation and M2b polarization under anti-inflammatory conditions strongly depend on functional IL-6 signaling in macrophages. The potential benefit of preconditioned MSCs and IL-6 should be considered for future clinical treatment.
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It is known that, following a physiological insult, bone marrow-derived mesenchymal stem cells (MSCs) mobilize and home to the site of injury. However, the effect of injury on the function of endogenous MSCs is unknown. In this study, MSCs harvested from the bone marrow of swine with or without acute respiratory distress syndrome (ARDS) were assessed for their characteristics and therapeutic function. ⋯ The results suggest that, following ARDS, there is an increase in the clonogenic capacity of MSCs to increase the available stem cell pool in vivo. However, MSCs harvested from subjects with ARDS seem to exhibit a diminished capacity to proliferate, express regenerative signals, and secrete pro/anti-inflammatory mediators.
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Skin injuries in horses frequently lead to chronic wounds that lack a keratinocyte cover essential for healing. The limited proliferation of equine keratinocytes using current protocols has limited their use for regenerative medicine. Previously, equine induced pluripotent stem cells (eiPSCs) have been produced, and eiPSCs could be differentiated into equine keratinocytes suitable for stem cell-based skin constructs. However, the procedure is technically challenging and time-consuming. The present study was designed to evaluate whether conditional reprogramming (CR) could expand primary equine keratinocytes rapidly in an undifferentiated state but retain their ability to differentiate normally and form stratified epithelium. ⋯ Our results prove that conditional reprogramming is the first method that allows for the rapid and continued in vitro propagation of primary equine keratinocytes. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. This offers the opportunity for treating recalcitrant horse wounds using autologous transplantation.
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Replacement therapy for hemophilia remains a lifelong treatment. Only gene therapy can cure hemophilia at a fundamental level. The clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) system is a versatile and convenient genome editing tool which can be applied to gene therapy for hemophilia. ⋯ PBMNCs are good somatic cell choices for generating iPSCs from hemophilia patients. The iPSC technique is a good tool for genetic therapy for human hereditary diseases. CRISPR-Cas9 is versatile, convenient, and safe to be used in iPSCs with low off-target effects. Our research offers new approaches for clinical gene therapy for hemophilia.