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HPP-CFC

[high proliferative potential colony-forming cells] These cells have been defined by their ability to form very large colonies (> 5 mm in diameter) in bone marrow cell cultures (see: BMC) (see also: Colony formation assay) containing approximately 50,000 cells, including progenitor and mature hematopoietic cells of the lineage of granulocytes, macrophages, and megakaryocytes, including CFU-GEMM (see also: Hematopoietins, Hematopoiesis). See also: HPP-Q for such colony-forming cells obtained by growth under conditions blocking the activities of TGF-beta-1.

Cells that give rise to colonies smaller than 1 mm in these assays are usually referred to as low proliferative potential colony-forming cells (abbr. LPP-CFC). These primitive hematopoietic stem cells are considered to comprise cell types such as BFU-E and CFU-GM.

HPP-CFCs have been divided into three different classes (HPP-CFC-1, HPP-CFC-2, HPP-CFC-3) in order of primitiveness. They are relatively resistant to treatment in vivo with the cytotoxic drug Fluorouracil or 4-HC (4-hydroperoxycyclophosphamide) and have been shown to correlate with cells capable of repopulating the bone marrow of lethally irradiated mice (see also: MRA, marrow repopulating ability, for an assay system).

HPP-CFC, unlike LTC-IC (long-term culture-initiating cells), are not considered to be a measure of true pluripotential hematopoietic stem cells but, rather, of their slightly more differentiated progeny (primitive hematopoietic progenitor cells, abbr. PHPC). It has been suggested that Blast colony-forming cells resemble the most primitive HPP-CFC type. Numbers of HPP-CFCs can be determined by Limiting dilution analysis.

It has been shown that TGF-beta is a direct selective inhibitor of murine and human HPP-CFC. Various combination of cytokines have been shown to promote the expansion of HPP-CFC in liquid cultures (see: Delta assay) with IL1, IL6, and SCF, alone or in combination, or SCF + IL3, being the most effective.

SCF in particular has been shown to synergistically interact with a number of cytokines at suboptimal concentrations to directly augment the proliferative capacity of HPP-CFC. Survival of HPP-CFC is increased by flt-3 ligand. Under conditions of direct cell-to-cell contact jagged-2 also promotes proliferation of HPP-CFC.

The presence of lithium in Dexter-type long-term BMC (bone marrow culture) has been shown to stimulate HPP-CFC, probably by induction of multiple growth factors from stromal cells. WECHE reduces the production of high proliferative potential colony-forming cells (HPP-CFC) from fetal liver-derived stem cells.

See also 47.10, which is a transgenic cell line yielding HPP-CFC.

For other entries pertaining to hematopoiesis see also the Hematology Dictionary section of this encyclopedia. For an overview of other cell lines used in research on cytokines see: Cell lines in Cytokine Research. For other relevant entries see also: Cell types.

LAST MODIFIED: January 2002

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