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a murine stomal cell line established from newborn B6C3F1 op/op mouse calvaria (Kodama et al, 1994). These cells do not produce functional M-CSF due to the osteopetrotic mutation in the gene encoding M-CSF.

Coculture of OP9 cells with mouse embryonic stem cells (ES cells) has been used to develop an efficient differentiation induction system allowing preferential differentiation of ES cells into hematopoietic cells other than the lineage of monocytes and macrophages (see also: hematopoiesis) (Nakano, 1995; Suwabe et al, 1998; Kitajima et al, 2003; Nakayama et al, 1998; Suzuki and Nakano, 2001). The OP9 system does not require any exogenous growth factors or a complex embryoid structure for the induction.

ES cells cocultured on OP9 cells give rise to embryonic primitive erythrocytes, and then adult type definitive erythrocytes with a time course similar to that seen in murine ontogeny (Nakano et al, 1996). GATA-1 regulates growth and differentiation of definitive erythroid lineage cells during in vitro differentiation of ES cells (Suwabe et al, 1998).

Coculture of OP9 cells with ES cells also gives rise to myeloid and B-lineage cells. The presence of M-CSF has an inhibitory effect on the differentiation of ES cells to blood cells other than macrophages.

The kit receptor, the ligand of which is SCF, has been shown to play an important role not only in the proliferative response of hematopoietic stem cells but also in their adhesion to OP9 stromal cells.

Culture of OP9 cells with a combination of EGF, SCF, and the chemically defined medium mSFO2 has been shown to provide a microenvironment where kit(+), Thy1(+/low), Mac-1(+/low), B220(-), TER-119(-), common beta(+), IL2 receptor (+) gp130(+) cells are selectively propagated from normal, unfractionated bone marrow cells (Takakura et al, 1996). In a colony formation assay this cell population produces colonies at a very high efficiency (50 %) but the cells have only limited proliferative ability in an irradiated recipient. The cells might represent colony-forming units in culture (CFU-c) with short-term bone marrow reconstituting ability.

Lieber et al (2003, 2004) have described the utilization of OP9 cells for the in vitro differentiation of mouse embryonic stem cells into neutrophils. Schmitt and Zuniga-Pflucker (2002) have described an in vitro culture system that is able to generate mature T-cells from fetal liver stem cells by expressing the Notch ligand delta-like-1 (dll1) on the OP9 stromal cell line (Lehar and Bevan, 2002).

Ueno et al (2003) have reported that OP9 cells express a mammalian homolog of the Drosophila melanogaster gene KIRRE, which is involved in the hematopoietic supportive capacity of OP9 mouse stromal cells.

Gao et al (2010) have reported that OP9 cells have the immunophenotype CD45(-), CD11b(-), flk-1(-), CD31(-), CD34(-), CD44(+), CD29(+), Sca-1(+), CD86(-) identical to canonical mouse mesenchymal stem cells. The expression of CD140a, CD140b, alpha-smooth muscle actin, and Calponin suggest the perivascular origin of the cells. Functionally, OP9 cells have strong clonogenic ability and can be induced into osteocytes, chondrocytes and adipocytes. OP9 cells can suppress T-lymphocyte proliferation stimulated by nonspecific mitogens (PHA) or allogeneic lymphocytes (BALB/c T-cells). Migration of OP9 cells can be induced efficiently by bFGF, IGF-1, IL3, PDGF-BB, TGF-beta-1 and TGF-beta-3.

For an overview of other cell lines used in research on cytokines see: Cell lines in Cytokine Research. For other related/relevant entries see also: Cell types.

Copyright 2012 by H IBELGAUFTS. All rights reserved.


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