Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells

Abstract

Relative levels of cytoplasmic aldehyde dehydrogenase (ALDH) were determined in selected subpopulations of normal human bone marrow cells using a flow cytometric assay that simultaneously detects a cell surface antigen (as a marker of cell lineage and developmental stage) and the level of ALDH. The intracellular level of this enzyme has been shown to be directly related to cellular resistance to activated cyclophosphamide and is believed to be important in the survival of cells capable of repopulating marrow in autologous bone marrow transplant procedures. Western blot analysis and flow cytometric analysis of four murine cell lines with known ALDH levels were used to establish the relation between ALDH content and fluorescence with an affinity-purified anti-mouse ALDH antibody. An affinity purified anti- human ALDH antibody, characterized by immunoblotting of cytosolic extracts of cell lines with known ALDH content, was used to determine relative ALDH levels in the marrow subpopulations. We found that hematopoietic progenitor cells express the highest level of ALDH, while lymphocytes express the lowest level. Immature erythroid cells express ALDH at a level intermediate between progenitor cells and lymphocytes.

Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance

“…Recent studies have shown that several stem cell types, including hematopoietic stem cells and neural stem cells, possess high ALDH activity. (15) Moreover, ALDH is upregulated in several types of CSC. (27,28) Therefore, ALDH has been used as a stem cell marker.…”

“…(14) We also focused on ALDH, another stem cell marker, that plays a key role in aldehyde metabolism. Several stem cell types, including hematopoietic stem cells (15) and neural stem cells, (16) possess high ALDH activities. We found that ALDH was upregulated in TEC compared with that in NEC.…”

Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation

“…One promising strategy is to identify HSC and progenitors based on an enzymatic activity that is expressed at relatively high levels in primitive haematopoietic cells. A variety of studies using immunohistochemical and enzymatic assays have demonstrated that aldehyde dehydrogenase (ALDH) is highly expressed in primitive haematopoietic cells, suggesting that this enzyme may be a useful target for identifying HSC and progenitors (Kohn & Sladek, 1985;Sahovic et al, 1988;Kastan et al, 1990;Jones et al, 1995Jones et al, , 1996Niederreither et al, 1999). In support of this, Jones et al (1996) demonstrated that primitive murine bone marrow cells that expressed high levels of ALDH could be enriched using a fluorescent substrate of ALDH, termed dansyl-aminoacetaldehyde.…”

Bone Marrow–Derived Aldehyde Dehydrogenase–Bright Stem and Progenitor Cells for Ischemic Repair

“…11 ALDH br cells comprise 0.5% to 5% of nucleated cells in human umbilical cord blood, cytokine-mobilized (eg, G-CSF) peripheral blood stem cells, and bone marrow, and they are highly enriched for stem and progenitor cells of multiple lineages. [11][12][13][14] Early work on ALDH br cells focused on bone marrow and umbilical cord blood hematopoietic lineages. ALDH br cells have high hematopoietic progenitor activity, and their key attributes are their ability to establish long-term, multilineage hematopoietic colonies and to engraft long term.…”