title: Effects of long-term hypoxia and pro-survival cocktail in bone marrow-derived stromal cell survival.
abstract: The goal of this study was to determine whether a pro-survival cocktail (PSC, consisting of IGF-1, Bcl-XL, and Caspase-I Inhibitor) and long-term hypoxia (LTH) enhance survival and functional properties of bone marrow-derived stromal stem cells (BMSCs), in response to stress conditions. PSC-treated cells retained BMSC surface markers and protected cells from apoptosis under serum starvation and ischemic (1% O2 and 100 μM H2O2) conditions. LTH promoted osteogenesis, while suppressing adipogenesis. LTH alone did not result in an improvement in the apoptosis rate; however, PSC conferred significant protection regardless of the oxygenation status. One of the possible mechanisms of PSC protection was due to the elevated phospho-AKT in treated groups. PSC treatment or LTH did not alter migration toward stem cell-derived factor-1 alpha (SDF-1α) or fetal bovine serum, nor did they enhance cell motility during wound healing. There was no difference in the secreted cytokine profiles of BMSCs treated with PSC after stress when grown in normoxic or LTH. However, LTH did upregulate the vascular endothelial growth factor, hepatocyte growth factor, and SDF-1α, while it downregulated other anti- and proinflammatory cytokines and chemokines. We also observed a high degree of interdonor BMSC variability in response to pretreatment with PSC and LTH, confounding the functional results, underscoring the observation that not all donor-derived BMSCs will respond similarly.
authors.affiliation: 1 Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health , Bethesda, Maryland.
authors.forename: Saejeong
authors.initials: S
authors.lastname: Kim
authors.forename: Aneeka
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Inae
authors.initials: I
authors.lastname: Lee
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D061945:Caspase Inhibitors / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage; D010012:Osteogenesis / Q000187:drug effects*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D051020:bcl-X Protein / Q000008:administration & dosage
chemical_list: D061945:Caspase Inhibitors; D051020:bcl-X Protein; D007334:Insulin-Like Growth Factor I