A human peripheral blood monocyte-derived subset acts as pluripotent stem cells

Abstract

We have identified, cultured, characterized, and propagated adult pluripotent stem cells (PSC) from a subset of human peripheral blood monocytes. These cells, which in appearance resemble fibroblasts, expand in the presence of macrophage colony-stimulating factor and display monocytic and hematopoietic stem cell markers including CD14, CD34, and CD45. We have induced these cells to differentiate into mature macrophages by lipopolysaccharide, T lymphocytes by IL-2, epithelial cells by epidermal growth factor, endothelial cells by vascular endothelial cell growth factor, neuronal cells by nerve growth factor, and liver cells by hepatocyte growth factor. The pluripotent nature of individual PSC was further confirmed by a clonal analysis. The ability to store, expand, and differentiate these PSC from autologous peripheral blood should make them valuable candidates for transplantation therapy. P luripotent stem cells (PSC) are a valuable resource for research, drug discovery, and transplantation (1, 2). These cells or their mature progeny can be used to study differentiation processes, identify and test lineage-specific drugs, or replace tissues damaged by a disease. However, the use of PSC from human fetuses, umbilical cords, or embryonic tissues derived from in vitro fertilized eggs raises ethical and legal questions, poses a risk of transmitting infections, and͞or may be ineffective because of immune rejection. A way to circumvent these problems is by exploiting autologous stem cells, preferably from an accessible tissue. In this context, it has been reported that bone marrow contains cells that appear to have the ability to transdifferentiate into mature cells belonging to distinct cell lineages (2). A recent study indicated that bone marrow mesenchymal PSC can be expanded in vitro and after transplantation differentiate in vivo into cells belonging to distinct lineages (3). Other studies have, however, raised the possibility that such mature cells may result from fusion of stem cells with mature resident tissue cells (4,5).In the present studies, we have described the characterization and expansion in vitro of a yet unidentified subset of human peripheral blood monocytes that behave as PSC. We have shown that these cells can be induced to acquire macrophage, lymphocyte, epithelial, endothelial, neuronal, and hepatocyte phenotypes in the absence of a fusion with preexisting mature tissue cells. The ability to obtain these PSC from an easily accessible source such as peripheral blood and to store them in liquid nitrogen should make them valuable candidates for autologous transplantation. Materials and MethodsCell Culture. Monocytes were obtained from buffy coats (each from 500 ml of peripheral blood) of healthy individuals (LifeSource Blood Services, Glenview, IL) by using a selective attachment procedure as described (6, 7). Fresh mononuclear cells for this procedure and͞or after storage in liquid nitrogen in FBS (Harlan Breeders, Indianapolis) containing 10% dimethyl sulfoxide (Sigma) were obtained after Ficoll-...

Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells

“…However, these cells have limited HUMAN PERIPHERAL BLOOD DERIVED MESENCHYMAL STEM CELLS growth potential. 25 To circumvent this problem, the use of BM mobilization in patients has been described in many literatures. 12,26 This technique involves the stimulation of BM using G-CSF treatment followed by the harvesting of progenitor cells from 1 ml of PB subjected to leukapheresis.…”

Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

“…In healthy subjects, cells of monocyte lineage (other mesodermal-derived cells) can generate EC progenitors (Rehman et al, 2003) or act as pluripotent stem cells (Zhao et al, 2003). They can develop an EC phenotype, especially when stimulated by VEGF and/or bFGF (Fernandez Pujol et al, 2000;Zhao et al, 2003), and produce a functional capillary-like mesh (Schmeisser et al, 2001) permeable by blood cells (Anghelina et al, 2004), hence recapitulating embryo vasculogenesis (Risau et al, 1988).…”

“…They can develop an EC phenotype, especially when stimulated by VEGF and/or bFGF (Fernandez Pujol et al, 2000;Zhao et al, 2003), and produce a functional capillary-like mesh (Schmeisser et al, 2001) permeable by blood cells (Anghelina et al, 2004), hence recapitulating embryo vasculogenesis (Risau et al, 1988). Unlike these reports on the vascular ability by monocytes, mature macrophages have been found to form capillary-like lumina and branching patterns in vitro, confirming their propensity to participate to the de novo formation of microvessels (Anghelina et al, 2006b).…”

Pluripotent plasticity of stem cells and liver repopulation

“…Adult stem cells have been found in the BM, peripheral blood, umbilical cord, liver, skin, gastrointestinal tract, pancreas, cornea and retina of the eye, and the dental pulp of teeth. 1,[15][16][17][18] …”