Hepatocyte-like cells derived from human amniotic epithelial, bone marrow, and adipose stromal cells display enhanced...

Transplantation of primary hepatocytes has been used in treatments for various liver pathologies and end-stage liver disease. However, shortage of donor tissue and the inability of hepatocyte proliferation in vitro have lead to alternative methods such as stem cell-derived hepatocyte-like cells (HLCs). Mesenchymal stromal/stem cells, and amniotic epithelial cells were isolated from human bone marrow (BM-MSCs), lipoaspirates (ASCs), and amniotic tissue (AECs) respectively. All cells were differentiated into HLCs on plates coated with Type I collagen or Porcine Liver Extracellular Matrix (PLECM-AA) matrix. Flow cytometry of BM-MSCs and ASCs, and AECs showed high expression of MSC-specific and embryonic stem cell markers respectively. All cell types differentiated into osteocytes, chondrocytes, and adipocytes. All cell type-derived HLCs presented the typical cuboidal primary hepatocyte morphology on PLECM-AA and fewer vacuoles (AECs) compared to HLCs cultured on type I collagen. Gene analysis of all cell type-derived HLCs cultured on PLECM-AA revealed higher upregulation of genes involved in drug transportation and metabolism compared to HLCs cultured on type I collagen. Although, HLCs cultured on PLECM-AA displayed some hepatocyte-related function and bioactivity, overall gene expression was lower compared to that of primary hepatocytes suggesting that caution should be taken when considering using HLCs to replace total hepatocyte functionality.