title: Biology of umbilical cord blood progenitors in bone marrow niches.
abstract: Within the bone marrow (BM), hematopoietic progenitor cells (HPCs) are localized in poorly oxygenated niches where they interact with the surrounding osteoblasts (OBs) through VLA4/VCAM-1 engagement, and are exposed to interleukin-6 (IL-6), stem cell factor (SCF), and chemokines such as CXCL12 (OB factors). Umbilical cord (UC) is more highly oxygenated that the BM microenvironment. When UC-HPCs are exposed to the 2% to 3% O(2) concentration found in the bone endosteum, their survival is significantly decreased. However, engagement of VLA-4 integrins on UCB-derived CD34(+) cells reduced cell death in 2% to 3% O(2) conditions, which was associated with an increase in phospho-Ser473 AKT and an increase in phospho-Ser9 GSK3b. Consistent with the role of GSK3b in destabilizing beta-catenin, there was more cytoplasmic beta-catenin in UC-HPCs exposed to 2% to 3% O(2) on fibronectin, compared with suspension culture. UC-HPCs cultured at 2% to 3% O(2) with OB factors showed an increase in nuclear beta-catenin and persistence of a small pool of CD34(+)38(-) HPCs. CFU assays followed by surface phenotyping of the plated colonies showed improved maintenance of mixed lineage colonies with both erythroid and megakaryocytic precursors. These studies provide a biologic perspective for how UC-derived HPCs adapt to the bone endosteum, which is low in oxygen and densely populated by osteoblasts.
authors: Stem Cell Institute, University of Minnesota Medical School, Minneapolis, USA.
authors: Mo A
authors: MA
authors: Dao
authors: Michael H
authors: MH
authors: Creer
authors: Jan A
authors: JA
authors: Nolta
authors: Catherine M
authors: CM
authors: Verfaillie
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D002450:Cell Communication; D002470:Cell Survival; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D039041:Integrin alpha4beta1 / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051176:beta Catenin / Q000032:analysis
chemical_list: D003598:Cytoskeletal Proteins; D039041:Integrin alpha4beta1; C512806:NIN protein, human; D009687:Nuclear Proteins; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen