Effect of Microenvironment on Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into HepatocytesIn VitroandIn Vivo

Abstract

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (P < 0.05). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo.

Differentiation Induction of Human Stem Cells for Corneal Epithelial Regeneration

“…Unfortunately, in some experiments, terminal differentiation was very low [ 104 ] or cannot be obtained [ 7 ]. Probably, the degree of differentiation after transplantation depends on the biological microenvironment at the transplantation sites which are difficult to be controlled [ 110 , 111 , 112 ].…”

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

“…& MSC affect the phenotype of M1 macrophages and promote their change into M2 [175]. & Mesenchymal cells isolated from the postnatal tissues reduce the cytokine storm phenomenon during acute and chronic liver damage, thus reducing the cell apoptosis and necrotic areas [133,142,157,158,176,177]. Acute injurysurgical BDL Decreased: fibronectin deposition, areas occupied by myofibroblasts, number of cells positive for S100A4, TGFβ pathway activation, αvβ6 integrin expression.…”

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source

“…Over the past decade, several studies have introduced protocols to induce hepatocyte-differentiation in stem cells; most methods use chemical and conditioned medium stimulations or coculture with other cell types to expedite hepatic differentiation from human bone marrow mesenchymal stem cells, human umbilical cord mesenchymal stem cells, and human iPSCs. [20][21][22][23] Induced hepatocyte-like cells (i-Hep) are shown to possess most of the normal hepatocyte functions (including the secretion of aminotransferases, albumin, and α-fetoprotein), functional biotransformation systems, and the ability to engraft, integrate, and proliferate in an injured liver. Nie et al 24 used human iPSC to generate a functional liver organoid, which exhibited stronger hepatic functions than human iPSC-derived hepatocytelike cells (or i-Hep).…”