title: Intra-osseous Co-transplantation of CD34-selected Umbilical Cord Blood and Mesenchymal Stromal Cells.
abstract: Human mesenchymal stromal cells (MSC) have been shown to support the growth and differentiation of hematopoietic stem cells (HSC). We hypothesized that intra-osseous (IO) co-transplantation of MSC and umbilical cord blood (UCB) may be effective in improving early HSC engraftment, as IO transplantation has been demonstrated to enhance UCB engraftment in NOD SCID-gamma (NSG) mice. Following non-lethal irradiation (300rads), 6 groups of NSG mice were studied: 1) intravenous (IV) UCB CD34+cells, 2) IV UCB CD34+cells and MSC, 3) IO UCB CD34+cells, 4) IO UCB CD34+cells and IO MSC, 5) IO UCB CD34+cells and IV MSC, and 6) IV UCB CD34+and IO MSC. Analysis of human-derived CD45+, CD3+, and CD19+cells 6 weeks following transplant revealed the highest level of engraftment in the IO UCB plus IO MSC cohort. Bone marrow analysis of human CD13 and CD14 markers revealed no significant difference between cohorts. We observed that IO MSC and UCB co-transplantation led to superior engraftment of CD45+, CD3+and CD19+lineage cells in the bone marrow at 6 weeks as compared with the IV UCB cohort controls. Our data suggests that IO co-transplantation of MSC and UCB facilitates human HSC engraftment in NSG mice.
authors.affiliation: Stem Cell Transplant Program, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Leland
authors.initials: L
authors.lastname: Metheny
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine; Angie Fowler AYA Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH 44106, USA.
authors.forename: Saada
authors.initials: S
authors.lastname: Eid
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Lingas
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Reese
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine; University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Meyerson
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tong
authors.affiliation: Stem Cell Transplant Program, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Case Western Reserve University School of Medicine; Angie Fowler AYA Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University School of Medicine; University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Huang
keywords: cord blood stem cell transplantatio; hematopoietic stem cell transplantation; mesenchymal stromal cells