Induced Pluripotent Stem Cells (Ipscs) Based Liver Organoid: the Benefits and Challenges.

The liver is the main metabolic organ and functions to regulate many physiological functions in the human body. Approximately 70% of liver mass consists of hepatic cells (hepatocytes), which execute the liver's metabolic processes. When liver damage progresses to a chronic condition, such as end-stage liver disease (ESLD) or cirrhosis of the liver, the patient's only option for therapy is organ transplantation if the supply of available transplanted organs is insufficient to meet the patient's needs. The fundamental objective of the search for alternatives to organ transplantation has been to make liver tissue replacement more accessible and to produce hepatic and bioartificial liver tissue. Multiple hepatic cell lineages can be formed from human-induced pluripotent stem cells (hiPSCs) from embryoid bodies to become mature hepatocytes. hiPSCs also show a promising source for manufacturing human liver spheroids and are made to produce three-dimensional hepatobiliary organoids, and in some ways, it also briefly highlights important features of early hepatogenesis. Unquestionably, the art of cell culture has evolved to include the use of organoid technology as a resource for learning human biology in the context of health and illness. Organoids are essentially miniature organs that can grow in a three-dimensional matrix to resemble genuine organs in terms of both structure and function. This review summarized alternative protocols to differentiate hepatocytes from iPSC and to produce liver organoids based on iPSC in various ways. The growth of human iPSCs into liver organoids has been accomplished using several procedures.

Conditioned medium of E17 rat brain cells induced differentiation of primary colony of mice blastocyst into neuron-like cells.

BACKGROUND: Conditioned medium is the medium obtained from certain cultured cells and contained secretome from the cells. The secretome, which can be in the form of growth factors, cytokines, exosomes, or other proteins secreted by the cells, can induce the differentiation of cells that still have pluripotent or multipotent properties. OBJECTIVES: This study examined the effects of conditioned medium derived from E17 rat brain cells on cells with pluripotent properties. METHODS: The conditioned medium used in this study originated from E17 rat brain cells. The CM was used to induce the differentiation of primary colonies of mice blastocysts. Primary colonies were stained with alkaline phosphatase to analyze the pluripotency. The morphological changes in the colonies were examined, and the colonies were stained with GFAP and Neu-N markers on days two and seven after adding the conditioned medium. RESULTS: The conditioned medium could differentiate the primary colony, beginning with the formation of embryoid-body-like structure; round GFAP positive cells were identified. Finally, neuron-like cells testing positive for Neu-N were observed on the seventh day after adding the conditioned medium. CONCLUSIONS: Conditioned medium from different species, in this case, E17 rat brain cells, induced and promoted the differentiation of the primary colony from mice blastocysts into neuron-like cells. The addition of CM mediated neurite growth in the differentiation process.

Heterogeneity of Cells Population and Secretome Profile of Differentiated Cells from E17 Rat Neural Progenitor Cells.

Conditioned medium has now gained increasing interest since the development of secretome-based therapy. Various types of cells have been studied as a source of the secretome. One of them is neural progenitor cells (NPCs). These are cells that capable of differentiating into neurons as well as glial cells. Indeed, the study on NPCs has risen in the last few decades, but the study on the differentiated cells has not clearly described. The most common procedures that widely used to get the conditioned medium is starvation. However, cell starvation may cause environmental stress and become an apoptotic trigger for the cells. In this study, we analyzed the effect of starvation on differentiated cells from E17 rat neural progenitor cells (NPCs) based on cells characteristics and secretome profile. We found that starvation decreased cells viability and affected the heterogeneity of the cell population. Astrocytes survived more under nutrient deprivation conditions, and the progenitor cells showed a higher tendency to differentiate to glial cells than neurons. Duration of starvation also influenced the secretome profile, alterations found in protein types and also their function in the biological process. During 24 hours of starvation, cells secreted proteins that were used to maintain cell growth, stimulate differentiation, and produce energy, but there were also proteins that identified and involved in autophagy activation. After 48 hours of starvation, astrocytes that became the dominant cells secreted proteins that try to keep protecting the remaining neurons.