Stem Cell Res Ther
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Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Despite advances in renal replacement therapies and organ transplantation, poor quality of life for dialysis patients and long transplant waiting lists remain major concerns for nephrologists treating this condition. There is therefore a pressing need for novel therapies to promote renal cellular repair and tissue remodeling. ⋯ Adverse effects observed following intravascular administration of MSCs include immune rejection, adipogenic differentiation, malignant transformation, and prothrombotic events. Nonetheless, most studies indicate a remarkable capability of MSCs to achieve kidney repair. This review summarizes the regenerative potential of MSCs to provide functional recovery from renal failure, focusing on their application and the current challenges facing clinical translation.
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Because of their pluripotent characteristics, human induced pluripotent stem cells (iPSCs) possess great potential for therapeutic application and for the study of degenerative disorders. These cells are generated from normal somatic cells, multipotent stem cells, or cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, NANOG, SSEA-3, SSEA-4, and REX1, and can differentiate into all adult tissue types, both in vitro and in vivo. ⋯ The later stage includes overcoming the barrier of reprogramming-induced senescence or cell-cycle arrest by shutting off the function of these tumor suppressor genes, followed by the induction of endogenous stemness genes for the full commitment of iPSCs (full-iPSCs). Thus, the reactive oxygen species (ROS) produced by oxidative stress might be critical for the induction of endogenous reprogramming-factor genes via epigenetic changes or antioxidant reactions. We also discuss the critical role of tumor suppressor genes in the evaluation of the tumorigenicity of human cancer cell-derived pluripotent stem cells, and describe how to overcome their tumorigenic properties for application in stem cell therapy in the field of regenerative medicine.
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Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. Current treatment of ALI/ARDS is primarily supportive, with lung protective ventilation and fluid conserving strategies. ⋯ Recent studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI/ARDS have shown promising results. This review focuses on existing studies that have tested the use of MSCs in models of ALI/ARDS, and the potential mechanisms underlying their therapeutic effects.
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Cellular therapy products are an emerging medical product class undergoing rapid scientific and clinical innovation worldwide. These products pose unique regulatory challenges both for countries with existing regulatory frameworks and for countries where regulatory frameworks for cellular therapy products are under development. The United States Food and Drug Administration (US FDA) has a history of productive working relationships with international regulatory authorities, and seeks to extend this to the cellular therapy field. The US FDA and its global regulatory counterparts are engaged in collaborations focused on the convergence of scientific and regulatory approaches, and the education of scientists, clinicians, regulators, and the public at large on the development of cellular therapies.