Functions and the Emerging Role of the Foetal Liver into Regenerative Medicine

Abstract

During foetal life, the liver plays the important roles of connection and transient hematopoietic function. Foetal liver cells develop in an environment called a hematopoietic stem cell niche composed of several cell types, where stem cells can proliferate and give rise to mature blood cells. Embryologically, at about the third week of gestation, the liver appears, and it grows rapidly from the fifth to 10th week under WNT/β-Catenin signaling pathway stimulation, which induces hepatic progenitor cells proliferation and differentiation into hepatocytes. Development of new strategies and identification of new cell sources should represent the main aim in liver regenerative medicine and cell therapy. Cells isolated from organs with endodermal origin, like the liver, bile ducts, and pancreas, could be preferable cell sources. Furthermore, stem cells isolated from these organs could be more susceptible to differentiate into mature liver cells after transplantation with respect to stem cells isolated from organs or tissues with a different embryological origin. The foetal liver possesses unique features given the co-existence of cells having endodermal and mesenchymal origin, and it could be highly available source candidate for regenerative medicine in both the liver and pancreas. Taking into account these advantages, the foetal liver can be the highest potential and available cell source for cell therapy regarding liver diseases and diabetes.

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

“…Immortalized cells were cultured in Opti-MEM medium supplemented with 10% FBS. In order to determine the HPC population, we compared the corresponding mRNA expression profile of genes encoding (1) HPCs and hepatic specific markers, such as α-fetoprotein ( AFP ), hepatocyte nuclear factor 4 α ( HNF4A ), and alanine aminotransferase ( ALAT ) [21]; (2) HPCs and cholangiocyte-specific markers ( SOX9 ) [22] and epithelial cell adhesion molecule ( EPCAM ) [16]; (3) adipose-derived mesenchymal stem cell (ASCs) markers, such as CD105 and CD90 [23]; as well as an endothelial cell specific marker, platelet and endothelial cell adhesion molecule 1 ( PECAM1 ) [24]. We found that similarly to whole liver tissue, cultured HPCs expressed HNF4A and ALAT.…”

Cytological, histochemical, and ultrastructural study of human foetal liver of various gestation with future implications in segmental resection: an anatomical perspective

“…The sole treatment available is using human umbilical cord mesenchymal stem cell-derived extracellular vesicles, but these have potential tumorigenic effects or trigger cancer in a patient through upregulating the Bcl‐2 oncogene or activating ERK1/2 phosphorylation [ 26 ]. The findings of the presents study will help the liver transplant surgeons to understand the cytoarchitecture of foetal liver and future researchers working on hepatic tissue engineering [ 27 , 28 ].…”

Hallmarks of the human intestinal microbiome on liver maturation and function

“…For example, during the 5-6 th week of gestation (10 mm embryo) the human fetal liver is colonized by hematopoietic progenitors, and by the 2 nd trimester of gestation approximately 60-70% of the hepatic parenchyma is populated by hematopoietic cells [7] (Figure 1a). Additionally, the fetal liver has often been described as a "cardiovascular tissue" [8], since it receives oxygenrich blood from the umbilical vein and shunts it via the ductus venosus to the inferior vena cava and then to the fetus's heart. Fetal hepatic metabolism is also incapable of matching adult levels.…”