In Vitro Differentiation of Embryonic and Adult Stem Cells into Hepatocytes: State of the Art

Stem cells are a unique source of self-renewing cells within the human body. Before the end of the last millennium, adult stem cells, in contrast to their embryonic counterparts, were considered to be lineage-restricted cells or incapable of crossing lineage boundaries. However, the unique breakthrough of muscle and liver regeneration by adult bone marrow stem cells at the end of the 1990s ended this long-standing paradigm. Since then, the number of articles reporting the existence of multipotent stem cells in skin, neuronal tissue, adipose tissue, and bone marrow has escalated, giving rise, both in vivo and in vitro, to cell types other than their tissue of origin. The phenomenon of fate reprogrammation and phenotypic diversification remains, though, an enigmatic and rare process. Understanding how to control both proliferation and differentiation of stem cells and their progeny is a challenge in many fields, going from preclinical drug discovery and development to clinical therapy. In this review, we focus on current strategies to differentiate embryonic, mesenchymal(-like), and liver stem/progenitor cells into hepatocytes in vitro. Special attention is paid to intracellular and extracellular signaling, genetic modification, and cell-cell and cell-matrix interactions. In addition, some recommendations are proposed to standardize, optimize, and enrich the in vitro production of hepatocyte-like cells out of stem/progenitor cells

Sport activities for children and adolescents: the Position of the European Academy of Paediatrics and the European Confederation of Primary Care Paediatricians 2023-Part 1. Pre-participation physical evaluation in young athletes

The European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Paediatricians (ECPCP) emphasize the importance of promoting healthy lifestyles within the pediatric population. Many health professionals have questions concerning adequate levels of physical activity for both the healthy pediatric population and for those who may have specific complications. Unfortunately, the academic literature that provides recommendations for participation in sport activities within the pediatric population that have been published during the last decade in Europe is limited and is mainly dedicated to specific illnesses or advanced athletes and not toward the general population. The aim of part 1 of the EAP and ECPCP position statement is to assist healthcare professionals in implementing the best management strategies for a pre-participation evaluation (PPE) for participation in sports for individual children and adolescents. In the absence of a uniform protocol, it is necessary to respect physician autonomy for choosing and implementing the most appropriate and familiar PPE screening strategy and to discuss the decisions made with young athletes and their families. This first part of the Position Statement concerning Sport Activities for Children and Adolescents is dedicated to healthy young athletes