Embedded Files
Organoids are miniature versions of organs grown from human stem cells in a laboratory dish. They mimic key features of a human organ's structure and function. body across multiple organ systems.
Organoids are miniature versions of organs grown from human stem cells in a laboratory dish. They mimic key features of a human organ's structure and function. body across multiple organ systems.
Human disease models have proven valuable for their ability to closely mimic disease patterns in vitro, permitting the study of pathophysiological features and new treatment options.
Organoids are miniature versions of organs grown from human stem cells in a laboratory dish. They mimic key features of a human organ's structure and function. body across multiple organ systems.
Organoids are miniature versions of organs grown from human stem cells in a laboratory dish. They mimic key features of a human organ's structure and function. body across multiple organ systems.
Human disease models have proven valuable for their ability to closely mimic disease patterns in vitro, permitting the study of pathophysiological features and new treatment options.
Organoids
Organoids
Since organoids replicate key structural and functional features of the corresponding in vivo organ, their stem cells of origin acquire phenotype and functions of mature cells. Thus, the application of organoids to regenerative medicine highlights the need to face the question of whether, among mature versus stem/progenitor cells, a determined cell source is better suitable for a specific clinical need. Some years ago, Forbes and Newsome presented a very conveyable paradigm according to which the different available cell sources should be tailored for the specific pathological conditions according to the specific and peculiar properties they are endowed with [81]. There is no conclusive evidence on the applicability of this paradigm since most of the clinical trial results were negative. The existence of multiple sources with multiple properties and the occurrence of different and variable clinical settings (liver cirrhosis, acute on chronic liver failure, acute liver failure, inborn errors of metabolism) require us to envision the new figure of the cell therapist hepatologist.
The state of art of regenerative medicine of liver reached a point where further rigorous preclinical studies and high quality RCTs are required. These efforts could determine a cell source when this will finally prove its efficacy. Foetal liver is the major candidate on the block. The foetal liver possesses a unique feature given the co-existence of endodermal and mesenchymal derived cells and is hypothetically the more useful and qualified largely available source to address the main areas (fibrosis remodeling and liver repopulation) required for an effective cure of liver cirrhosis. Moreover, it contains a population of pluripotent stem cells, the hBTSCs, and thus is the unique highly available source candidate contemporarily for the regenerative medicine of the liver and pancreas. However, researchers and clinical investigators in regenerative medicine of the liver should adopt rigorous clinical studies for the foetal liver, as done only recently concerning the use of autologous MSCs in cirrhotic patients. Moreover, preclinical studies should be solid and tailored to address the questions raised by the clinical trials. Importantly, repopulation of the liver and the proliferation and differentiation of transplanted cells should be investigated systematically in the tissues along different and long-term time points. Different experimental models should be evaluated to investigate specific etiopathogenetic features that may impact the outcomes of the cell therapy. For example, models of liver fibrosis are best candidate to study intrahepatic factors associated with the interactions and effects of transplantation of exogenous cells, while NAFLD/NASH models may reveal potential systemic factors impacting on the effects of exogenous cells transplanted into the liver.
Hepatocyte organoids can adopt either a proliferative or a metabolic state, depending on the culture conditions. Furthermore, the metabolic gene expression profile can be modulated based on the principles that govern liver zonation.
Liver regeneration
Liver regeneration
In contrast to the low turnover in the resting state, the liver has a unique regenerative capacity, which is crucial for maintaining liver mass following physical or chemical damage. The events that occur after partial hepatectomy (PHx) in rodents have been well described and serve as a basis for understanding the general principles of liver regeneration. Notably, regeneration following PHx is not dependent on a small subset of stem cells. Instead, the majority of hepatocytes are able to proliferate.
.
Liver recolonization models have demonstrated that hepatocytes have an unlimited regenerative capacity. However, in normal liver, cell turnover is very slow. All zones of the resting liver lobules have been equally implicated in the maintenance of hepatocyte and cholangiocyte populations in normal liver. The ability to generate or expand the appropriate cell type in vitro, thus providing an abundant supply of healthy donor cells, is the first essential step in making cell replacement therapy feasible. Recent breakthroughs in expanding primary hepatocytes in vitro while retaining their in vivo regenerative capacity represent a major milestone towards enabling hepatocyte transplantation. Furthermore, the ability to expand, cryopreserve and transport hepatocytes without compromising their quality would enable the creation of a biobank that would ensure the availability of (in vitro-expanded) donor materials for hepatocyte transplantation, thus resolving the issue of donor shortage. More importantly, autologous cell transplantation will become feasible, as novel gene editing techniques and hepatocyte-specific delivery meth- ods can be applied to patient-derived hepatocytes for ex vivo gene editing to restore disease-specific mutations. Although currently, the lack of long-term efficacy due to either insufficient engraftment or lack of long-term maintenance of donor cells in host livers may pose a major challenge in cell transplantation.
Contributions
Weng Chuan Peng, Lianne J. Kraaier, Thomas A. Kluiver, ...
Page updated
Google Sites
Report abuse