Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells

Abstract

Bone marrow stroma provides the microenvironment for hematopoiesis and is also the source of mesenchymal progenitors (mesenchymal or marrow stromal cells [MSC]) that may serve as long-lasting precursors for bone, cartilage, lung, and muscle. While several studies have indicated the differentiation potential of MSC, few studies have been performed on the cells themselves. In an attempt to further expand our knowledge on these cells, we have performed studies on their cell cycle, immuno- and adhesive-phenotype, ex vivo expansion, and differentiation properties. MSC cultures have been initiated from human bone marrow low-density mononuclear cells and maintained in the absence of differentiation stimuli and hematopoietic cells. The homogenous layer of adherent cells thus formed exhibits a typical fibroblastlike morphology, a population doubling time of 33 h, a large expansive potential, and cell cycle characteristics including a subset (20%) of quiescent cells. The antigenic phenotype of MSC is not unique, borrowing features of mesenchymal, endothelial, and epithelial cells. Together, MSC express several adhesion-related antigens, like the integrin subunits alpha4, alpha5, beta1, integrins alphavbeta3 and alphavbeta5, ICAM-1, and CD44H. MSC produce and functionally adhere to extracellular matrix molecules. When incubated under proper stimuli, MSC differentiate into osteoblasts or adipocytes. Taken together, these results demonstrate that adherent marrow-derived cells cultured in the absence of hematopoietic cells and differentiation stimulus give rise to a population of cells with phenotypical and functional features of mesenchymal progenitors. The existence of a subset of quiescent cells in MSC cultures seems to be extremely significant, since their number and properties should be enough to sustain a steady supply of cells that upon proliferation and commitment may serve as precursors for a number of nonhematopoietic tissues.

The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells

“…On the basis of the available criteria, the cells used in our experiments had the properties of BMSCs as described earlier. 12 Capability of migration and tumor-homing property of rat bone marrow-derived stem cells in vitro and in vivo In vitro transwell assay were performed to determine the tropism of BMSCs toward gliomas. We compared the capability of various glioma cell lines to stimulate the migration of BMSCs.…”

Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

“…To study adipogenic differentiation potential, cells were cultured as monolayers, allowed to become near confluent, and then incubated with DMEM-HG plus 10% FBS supplemented with 10 -3 mM dexamethasone, 0.5 mM isobutyl methylxanthine, 0.2 mM indomethacin, and 10 µg/ml insulin (Sigma) for 2 w. To demonstrate the presence of adipocytes, cytoplasmic inclusions of neutral lipids were stained with oil-red-O (Sigma) [22].…”

Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors

“…For example, CD34 has been reported to be present on vascular endothelial cells (Lin et al, 1995;Suda et al, 2000), thyroid interfollicular fibroblasts (Yamazaki and Eyden, 1997), tumorigenic cells (Ohtani et al, 1998), and marrow stromal cells (Waller et al, 1995). CD44 has been reported to be present on periosteal stromal cells (Ghilzon et al, 1999) and marrow mesenchymal progenitor cells (Conget and Minguell, 1999). CD51 and CD56 have been reported to be present on the endosteal cells of bone marrow (Sillaber et al, 1999).…”