title: Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging.
abstract: The standard approach to assess hematopoietic stem cell (HSC) engraftment in experimental bone marrow transplantation models relies on detection of donor hematopoietic cells in host bone marrow following death; this approach provides data from only a single time point after transplantation for each animal. In vivo bioluminescence imaging was therefore explored as a method to gain a dynamic, longitudinal profile of human HSC engraftment in a living xenogeneic model. Luciferase expression using a lentiviral vector allowed detection of distinctly different patterns of engraftment kinetics from human CD34+ and CD34+CD38- populations in the marrow NOD/SCID/beta 2mnull mice. Imaging showed an early peak (day 13) of engraftment from CD34+ cells followed by a rapid decline in signal. Engraftment from the more primitive CD34+CD38- population was relatively delayed but by day 36 increased to significantly higher levels than those from CD34+ cells (P <.05). Signal intensity from CD34+CD38-engrafted mice continued to increase during more than 100 days of analysis. Flow cytometry analysis of bone marrow from mice after death demonstrated that levels of 1% donor cell engraftment could be readily detected by bioluminescence imaging; higher engraftment levels corresponded to higher image signal intensity. In vivo bioluminescence imaging provides a novel method to track the dynamics of engraftment of human HSC and progenitors in vivo.
authors.affiliation: Division of Research Immunology/BMT, Department of Radiology, and Congresman Dixon Cellular Imaging Core, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027,USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Rosol
authors.forename: Shundi
authors.initials: S
authors.lastname: Ge
authors.forename: Denise
authors.initials: D
authors.lastname: Peterson
authors.forename: George
authors.initials: G
authors.lastname: McNamara
authors.forename: Harvey
authors.initials: H
authors.lastname: Pollack
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
authors.forename: Marvin D
authors.initials: MD
authors.lastname: Nelson
authors.forename: Gay M
authors.initials: GM
authors.lastname: Crooks
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D002455:Cell Division; D002465:Cell Movement; D005434:Flow Cytometry; D017930:Genes, Reporter; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D008156:Luciferases