title: Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord blood stem and progenitor cells at 4°C.
abstract: We analyzed the effect of exposure to hypoxic/hypercapnic (HH) gas mixture (5% O2 /9% CO2 ) on the maintenance of functional cord blood CD34(+) hematopoietic stem and progenitor cells in severe hypothermia (4°C) employing the physiological and proteomic approaches. Ten-day exposure to HH maintained the Day 0 (D-0) level of hematopoietic stem cells as detected in vivo on the basis of hematopoietic repopulation of immunodeficient mice-short-term scid repopulating cells (SRC). Conversely, in the atmospheric air (20% O2 /0.05% CO2 ), usual condition used for cell storage at 4°C, stem cell activity was significantly decreased. Also, HH doubled the survival of CD34(+) cells and committed progenitors (CFCs) with respect to the atmospheric air (60% vs. 30%, respectively). Improved cell maintenance in HH was associated with higher proportion of aldehyde dehydrogenase (ALDH) positive cells. Cell-protective effects are associated with an improved maintenance of the plasma and mitochondrial membrane potential and with a conversion to the glycolytic energetic state. We also showed that HH decreased apoptosis, despite a sustained ROS production and a drop of ATP amount per viable cell. The proteomic study revealed that the global protein content was better preserved in HH. This analysis identified: (i) proteins sensitive or insensitive to hypothermia irrespective of the gas phase, and (ii) proteins related to the HH cell-protective effect. Among them are some protein families known to be implicated in the prolonged survival of hibernating animals in hypothermia. These findings suggest a way to optimize short-term cell conservation without freezing.
authors.affiliation: Etablissement Français du Sang Aquitaine-Limousin, Bordeaux, France; UMR 5164 CNRS/Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Marija
authors.initials: M
authors.lastname: Vlaski
authors.forename: Luc
authors.initials: L
authors.lastname: Negroni
authors.forename: Milica
authors.initials: M
authors.lastname: Kovacevic-Filipovic
authors.forename: Christelle
authors.initials: C
authors.lastname: Guibert
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunet de la Grange
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Rossignol
authors.forename: Jean
authors.initials: J
authors.lastname: Chevaleyre
authors.forename: Pascale
authors.initials: P
authors.lastname: Duchez
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.forename: Vincent
authors.initials: V
authors.lastname: Praloran
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Schmitter
authors.forename: Zoran
authors.initials: Z
authors.lastname: Ivanovic
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D010100:Oxygen / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D002245:Carbon Dioxide; D010100:Oxygen