Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity

Christ, Oliver; Lucke, Kai; Imren, Suzan; Leung, Karen; Hamilton, Melisa J.; Eaves, Allen C.; Smith, Clay; Eaves, Connie J.

doi:10.3324/haematol.11366

Cited by 81 publications

(68 citation statements)

References 46 publications

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“…Using ALDEFLUOR staining of live cells, combined with low side scatter (an indication of undifferentiated cells with few organelles and protrusions), clonogenic, multipotential stem/progenitor cells have been isolated, eg from mouse CNS [50], human bone marrow [51] and cord blood [52]. As expected, high expression of ALDH can be detrimental to tumour eradication; cyclophosphamide treatment of human colonic xenografts enriches for CD44 + ALDH + cells, and these double-positive cells are more tumourigenic than cells selected by solely CD44-positivity [53].…”

Section: Cytoprotective Strategiesmentioning

confidence: 99%

“…Alternatives to CD34 may include the expression of CD133 (CD133/1 = AC133) [77] and ALDH. HSCs with long-term repopulating ability have been identified in bone marrow and cord blood, based on the combined expression of CD34 and ALDH [51,52]. High ALDH expression has also been combined with CD133 to select for human HSCs from bone marrow [78].…”

Section: Bone Marrowmentioning

confidence: 99%

See 1 more Smart Citation

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Section: Cytoprotective Strategiesmentioning

confidence: 99%

Section: Bone Marrowmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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“…Attempts to quantify earlier progenitors that possess high proliferative and functional capacity have led to the application of ALDH quantification in CB transplantation. Christ et al 35 have demonstrated subpopulations of CD34, CD133 and ALDH expressing stem cells in human CB. HSC and most myeloid-restricted STRC as well as myeloid and lymphoid-restricted STRC are also ALDH þ , suggesting that selection of ALDH þ cells for clinical transplants will not necessarily have an adverse effect on myeloid recovery with ALDH activity serving as the best predictor for longterm engraftment.…”

Section: Introductionmentioning

confidence: 99%

“…A third population was lymphoid-restricted STRC. 35 These stem cells enumerated by in vitro short-term cultures were shown to influence engraftment in the early 1990s. Later, long-term cell cultures became available and led to estimation of stem cell numbers responsible from long-term repopulation.…”

Section: Introductionmentioning

confidence: 99%

Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic?

Beksaç

Preffer

2011

Bone Marrow Transplant

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In the clinical practice of hematopoietic SCT, the minimum numbers of cells required for a successful engraftment are defined on the basis of their CD45 and CD34 expression profiles. However, the quantity of earlier progenitors or CD34-positive cells at different differentiation stages within stem cell grafts is not generally taken into consideration. During the last decade, various teams have quantified the number of cells expressing various combinations of CD34, CD38, CD133, CD90 co-expression and/or aldehyde dehydrogenase functional capacity using flow cytometry. Some of these studies resulted in the greater appreciation that combinations of these Ags were associated with varied myeloid, erythroid and platelet engraftment rates whereas others showed that the relative absence or presence of these markers could define cells responsible for either short-or long-term engraftment. These findings were also extended to differences between progenitor cell populations found within BM vs peripheral or cord-blood grafts. Cells harvested from donors are also generally frozen and stored; thawed cells have variable levels of viability and functional capacity based on the time tested post thaw, which also can be assessed by flow cytometry. Finally, flow cytometry has the potential for analysis of cells carrying a mesenchymal stem cell phenotype, which may be quiescent within some of the stem cell products. This review will address the need for stem cell subpopulation quantification and summarize existing published data to identify some Ags and functional characteristics that can be applicable to daily clinical practice.

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“…Inhibition of ALDH enzyme, using the dimethylaminobenzaldehyde (DEAB) inhibitor, promotes HSC self-renewal via the reduction of retinoic acid activity, demonstrating that ALDH is a key regulator of HSC differentiation [14]. The ALDEFLUOR (Stem Cell Technologies, Grenoble, France, http://www.stemcell.-com) technique has recently been developed to quantify ALDH activity level in viable cells [15,16]. Using ALDE-FLUOR BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-5-proprionic acid)-aminoacetaldehyde (BAAA), a fluorescent synthetic substrate of ALDH, it is possible to isolate HSCs/HPCs using fluorescence-activated cell sorting (FACS) [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Dual SP/ALDH Functionalities Refine the Human Hematopoietic Lin−CD34+CD38− Stem/Progenitor Cell Compartment

et al. 2009

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Identification of prevalent specific markers is crucial to stem/ progenitor cell purification. Determinants such as the surface antigens CD34 and CD38 are traditionally used to analyze and purify hematopoietic stem/progenitor cells (HSCs/HPCs). However, the variable expression of these membrane antigens poses some limitations to their use in HSC/HPC purification. Techniques based on drug/stain efflux through the ATP-binding cassette (ABC)G2 pump (side population [SP] phenotype) or on detection of aldehyde dehydrogenase (ALDH) activity have been independently developed and distinguish the SP and ALDH Bright (ALDH Br ) cell subsets for their phenotype and proliferative capability. In this study, we developed a multiparametric flow cytometric method associating both SP and ALDH activities on human lineage negative (Lin 2 ) bone marrow cells and sorted different cell fractions according to their SP/ALDH activity level. We find that Lin 2 CD34 1 CD38 Low/2 cells are found throughout the spectrum of ALDH expression and are enriched especially in ALDH Br cells when associated with SP functionality (SP/ALDH Br fraction). Furthermore, the SP marker identified G 0 cells in all ALDH fractions, allowing us to sort quiescent cells regardless of ALDH activity. Moreover, we show that, within the Lin 2 CD34 1 CD38 2 ALDH Br population, the SP marker identifies cells with higher primitive characteristics, in terms of stemness-related gene expression and in vitro and in vivo proliferative potential, than the Lin 2 CD34 1 CD38 2 ALDH Br main population cells. In conclusion, our study shows that the coexpression of SP and ALDH markers refines the Lin 2 CD34 1 CD38 2 hematopoietic compartment and identifies an SP/ALDH Br cell subset enriched in quiescent primitive HSCs/HPCs.

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Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity

Cited by 81 publications

References 46 publications

Attributes of adult stem cells

Attributes of adult stem cells

Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic?

Dual SP/ALDH Functionalities Refine the Human Hematopoietic Lin−CD34+CD38− Stem/Progenitor Cell Compartment

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