Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells

Abstract

Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21-day cultures expressed ALB, and the ALB + cells coexpressed hepatocyte lineage markers. The ALB-expressing cells were able to proliferate in the culture system. Moreover, in the cell-transplantation model into liver-injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB-derived cell transplantation as a novel therapeutic option for liver failure.

Peripheral blood cell separation through surface‐modified polyurethane membranes

“…13,14 Hematopoietic stem cells as well as several other stem and progenitor cells are found in bone marrow 26,27 and umbilical cord blood. 28,29 Most current research on the use of stem cells in tissue engineering has focused on the development of tissue and organs from specific stem cells. 27,29 Safe and simple separation and purification of specific stem or mesenchymal stem cells from bone marrow or umbilical cord blood are essential for this application.…”

“…28,29 Most current research on the use of stem cells in tissue engineering has focused on the development of tissue and organs from specific stem cells. 27,29 Safe and simple separation and purification of specific stem or mesenchymal stem cells from bone marrow or umbilical cord blood are essential for this application. Membrane separation can provide a more sanitary and simple isolation of these cells than FACS or other separation methods.…”

Epithelial Colonies Cultured from Human Explanted Liver in Subacute Hepatic Failure Exhibit Hepatocyte, Biliary Epithelial, and Stem Cell Phenotypic Markers

“…Studies have been undertaken mostly in rodents [7,9,[14][15][16][17], but in humans, bone marrow [8,[18][19][20], amniotic tissue [21], cord blood [22], and adult and fetal liver have been studied.…”

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

“…It is well known that CB-derived cells contribute to skeletal muscle (Gang et al, 2004;Brzoska et al, 2006), liver (Kakinuma et al, 2003;Newsome et al, 2003;Di Campli et al, 2004), neural tissue (Buzanska et al, 2002), and myocardium regeneration (Henning et al, 2004;Ma et al, 2005), and more importantly, recent multiorgan engraftment and differentiation has been achieved in goats after transplantation of human CB CD34 ϩ lin Ϫ cells (Zeng et al, 2006a). Furthermore, several groups of investigators described the presence of Oct-4 ϩ , Nanog ϩ , and SSEA-3/4 ϩ stem cells in human CB and umbilical cord matrix (Carlin et al, 2006).…”