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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-05-1432.
Submitted May 7, 2003
Accepted August 24, 2003
Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging
Xiuli Wang*, Michael Rosol, Shundi Ge, Denise Peterson, George McNamara, Harvey Pollack, Donald B Kohn, Marvin D Nelson, and Gay M Crooks
Division of BMT/Research Immunology, Childrens Hospital Los Angeles, Los Angeles, CA, USA
Department of Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, USA
Congressman Dixon Cellular Imaging Core, Childrens Hospital Los Angeles, Los Angeles, CA, USA
* Corresponding author; email: Xiwang{at}chla.usc.edu.
The standard approach to assess hematopoietic stem cell (HSC) engraftment in experimental bone marrow transplant models relies on detection of donor hematopoietic cells in host bone marrow following sacrifice; 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 of NOD/SCID/ 2mnull mice. Imaging showed an early peak (Day13) 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<0.05). 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 sacrifice 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.
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