2 research outputs found
The Potential Clinical Use of Stem/Progenitor Cells and Organoids in Liver Diseases
The liver represents the most important metabolic organ of the human body. It is evident that an imbalance of liver function can lead to several pathological conditions, known as liver failure. Orthotropic liver transplantation (OLT) is currently the most effective and established treatment for end-stage liver diseases and acute liver failure (ALF). Due to several limitations, stem-cell-based therapies are currently being developed as alternative solutions. Stem cells or progenitor cells derived from various sources have emerged as an alternative source of hepatic regeneration. Therefore, hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are also known to differentiate into hepatocyte-like cells (HPLCs) and liver progenitor cells (LPCs) that can be used in preclinical or clinical studies of liver disease. Furthermore, these cells have been shown to be effective in the development of liver organoids that can be used for disease modeling, drug testing and regenerative medicine. In this review, we aim to discuss the characteristics of stem-cell-based therapies for liver diseases and present the current status and future prospects of using HLCs, LPCs or liver organoids in clinical trials
Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases
Liver dysfunctions are classified into acute and chronic diseases, which
comprise a heterogeneous group of pathological features and a high
mortality rate. Liver transplantation remains the gold-standard therapy
for most liver diseases, with concomitant limitations related to donor
organ shortage and lifelong immunosuppressive therapy. A concept in
liver therapy intends to overcome these limitations based on the
secreted extracellular vesicles (EVs; microvesicles and exosomes) by
mesenchymal stem/stromal cells (MSCs). A significant number of studies
have shown that factors released by MSCs could induce liver repair and
ameliorate systemic inflammation through paracrine effects. It is well
known that this paracrine action is based not only on the secretion of
cytokines and growth factors but also on EVs, which regulate pathways
associated with inflammation, hepatic fibrosis, integrin-linked protein
kinase signaling, and apoptosis. Herein, we extensively discuss the
differential effects of MSC-EVs on different liver diseases and on
cellular and animal models and address the complex molecular mechanisms
involved in the therapeutic potential of EVs. In addition, we cover the
crucial information regarding the type of molecules contained in MSC-EVs
that can be effective in the context of liver diseases. In conclusion,
outcomes on MSC-EV-mediated therapy are expected to lead to an
innovative, cell-free, noninvasive, less immunogenic, and nontoxic
alternative strategy for liver treatment and to provide important
mechanistic information on the reparative function of liver cells