The fetal liver as cell source for the regenerative medicine of liver and pancreas

Abstract

Patients affected by liver diseases and diabetes mellitus are in need for sources of new cells to enable a better transition into clinic programs of cell therapy and regenerative medicine. In this setting, fetal liver is becoming the most promising and available source of cells. Fetal liver displays unique characteristics given the possibility to isolate cell populations with a wide spectrum of endodermal differentiation and, the co-existence of endodermal and mesenchymal-derived cells. Thus, the fetal liver is a unique and highly available cell source contemporarily candidate for the regenerative medicine of both liver and pancreas. The purpose of this review is to revise the recent literature on the different stem cells populations isolable from fetal liver and candidate to cell therapy of liver diseases and diabetes and to discuss advantages and limitation with respect to other cell sources.

Keywords: Fetal liver; biliary tree stem/progenitor cells; cell therapy; diabetes mellitus; hematopoietic stem cells; hepatic stem/progenitor cells; hepatoblasts; liver cirrhosis.

Figure 1

Location and phenotype of different stem cells populations isolatable from fetal liver at 18^th-22^nd gestational age. BTSCs, biliary tree stem/progenitor cells, HpSCs, hepatic stem/progenitor cells, HBs hepatoblasts. ‡Markers found on the cell surface (all others listed are intracellular). (-) Negative. Abbreviations: AFP, α-fetoprotein; ALB, albumin; CD, common determinant; CD133, prominin; CK, cytokeratin; CXCR4, CXC-chemokine receptor 4; EpCAM, epithelial cell adhesion molecule; FOXa2, forkhead box a2; HES1, a member of the basic helix-loop-helix family of transcription factors and a transcriptional repressor of genes requiring an HLH protein for their transcription; HNF, hepatocyte nuclear factor; ICAM1, intercellular adhesion molecule 1, IHH, Indian Hedgehog; LGR5, Leucine-rich repeat-containing G-protein coupled receptor 5 that binds to R-Spondin; NANOG, Nanog homeobox; NCAM, neural cell adhesion molecule; NGN3, neurogenin 3; PAX genes, trancription factors regulating development; PDX1, Pancreatic and duodenal homeobox 1; PROX1, Prospero homeobox protein 1; PTC1, patched 1; PTF1, a trimeric transcription factor essential for pancreas development; P450 cytochrome P450; SHH, Sonic Hedgehog; SOX, Sry-related HMG box; VEGFR2, vascular endothelial growth factor 2.