Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging.
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.
Wang
Xiuli
X
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.
Rosol
Michael
M
Ge
Shundi
S
Peterson
Denise
D
McNamara
George
G
Pollack
Harvey
H
Kohn
Donald B
DB
Nelson
Marvin D
MD
Crooks
Gay M
GM
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
D018952:Antigens, CD34; D008156:Luciferases