Aldehyde dehydrogenase activity as a marker for the quality of hematopoietic stem cell transplants

MV Lioznov, P Freiberger, N Kröger… - Bone marrow …, 2005 - nature.com
MV Lioznov, P Freiberger, N Kröger, AR Zander, B Fehse
Bone marrow transplantation, 2005nature.com
Taking advantage of fluorescent substrates for their metabolic marker aldehyde
dehydrogenase (ALDH), hematopoietic stem cells (HSC) were defined as SSC lo ALDH br–
reflecting their low orthogonal light scattering and bright fluorescence intensity in flow
cytometry. Based thereon, we investigated the usefulness of ALDH activity for characterizing
HSC graft quality, particularly under stress conditions. We first compared the expression of
ALDH vs CD34 in bone marrow and peripheral blood stem cell (PBSC) samples over 7 …
Summary
Taking advantage of fluorescent substrates for their metabolic marker aldehyde dehydrogenase (ALDH), hematopoietic stem cells (HSC) were defined as SSC lo ALDH br–reflecting their low orthogonal light scattering and bright fluorescence intensity in flow cytometry. Based thereon, we investigated the usefulness of ALDH activity for characterizing HSC graft quality, particularly under stress conditions. We first compared the expression of ALDH vs CD34 in bone marrow and peripheral blood stem cell (PBSC) samples over 7 days. We noted that (i) only ALDH activity but not CD34 expression strongly reflected colony-forming ability over time, and that (ii) PBSC grafts stored at room temperature lost most of their progenitor cells within just 48 h. We then retrospectively related ALDH and CD34 expression as well as granulocyte–macrophage colony-forming units (CFU-GM) potential for 19 cryopreserved allogeneic PBSC grafts to engraftment data. Strikingly, in all six patients who received markedly decreased numbers of SSC lo ALDH br cells, this was associated not only with almost complete loss of CFU-GM potential but also with delayed establishment/permanent absence of full hematopoietic donor cell chimerism, whereas all other patients showed early complete donor chimerism. In conclusion, we suggest to measure ALDH activity as a surrogate marker for HSC activity, and to transport and store PBSC under controlled cooling conditions.
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