Characterization of cells in the developing human liver

doi:10.1111/j.1432-0436.2005.00019.x

Differentiation

Volume 73, Issue 5, June 2005, Pages 249-260

https://doi.org/10.1111/j.1432-0436.2005.00019.x Get rights and content

Abstract

Human hepatic progenitor cells (HPCs) have been shown to co-express the hematopoietic stem cell (HSC) markers, CD117 and CD34. These cells differentiate not only into hepatocytes and cholangiocytes but also into pancreatic ductal and acinar cells under certain conditions. The fetal liver (FL) is rich in precursor/stem cells; however, little is known about (i) the markers expressed by liver cells during fetal development and (ii) whether an equivalent to the adult liver stem-like progenitors exists in the FL. Here, (i) FL tissue obtained from human 5–18-week-old fetuses were evaluated by means of flow cytometry, immunocyto-, and histochemistry for the emergence of cells expressing and co-expressing known hematopoietic, hepatic, and pancreatic cell markers, and (ii) isolated putative HPCs were phenotypically and molecularly characterized. We report that (i) red blood and endothelial cell precursors were most abundant in early gestation. Cells expressing HSC and pancreatic markers were found in the first trimester, while cells expressing hepatic markers appeared in the second trimester. Very few committed cells were present in FLs obtained early in the first trimester. In addition, cells expressing pancreatic markers co-expressed the HSC marker CD117. (ii) Isolated CD117+/CD34+/CD90− cells in vitro expressed both the genes and proteins for the hepatic markers such as albumin, alpha feto protein (AFP), α1-antitrypsin, and cytokeratin 19 (CK19).

Our study suggests that hepatoblast and ductal plate/bile duct development mainly occurs during the second trimester. FLs in gestation weeks 5–9 had the highest numbers of precursor cells and the least committed cells. Cells that differentiate into Alb+ or CK19+ can be isolated from early FLs and may be appropriate progenitors for establishing novel systems to investigate basic mechanisms for cell therapy.

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ORIGINAL ARTICLECharacterization of cells in the developing human liver

Abstract

J Hepatol

Gastroenterology

Sem Cell Dev Biol

Hepatology

Blood

Differentiation

Am J Pathol

J Hepatol

Lancet

Blood

Immunity

Hepatocytes from non-hepatic adult stem cells

Nature

Chronic exposure to tumor necrosis factor in vivo alters the function of liver T lymphocytes in patients with primary sclerosing cholangitis

Gut

Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis

Am J Pathol

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

Proc Natl Acad Sci USA

A bipotential precursor population for pancreas and liver within the embryonic endoderm

Development

Development of the adult endocrine pancreas during metamorphosis in the sea lamprey, Petromyzon marinus L. II. Electron microscopy and immunocytochemistry

Anat Rec

ORIGINAL ARTICLE
Characterization of cells in the developing human liver