Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging

• Published in: Blood 2003-11, Vol.102 (10), p.3478-3482
• Main Authors: Wang, Xiuli, Rosol, Michael, Ge, Shundi, Peterson, Denise, McNamara, George, Pollack, Harvey, Kohn, Donald B., Nelson, Marvin D., Crooks, Gay M.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antigens, CD34; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Division; Cell Movement; Flow Cytometry; Genes, Reporter; Graft Survival; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - metabolism; Humans; Immunohistochemistry; Luciferases - analysis; Luciferases - genetics; Luminescent Measurements; Medical sciences; Mice; Mice, SCID; Microscopy, Fluorescence; Transduction, Genetic; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Heterologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-05-1432

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/β2mnull 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. (Blood. 2003;102: 3478-3482)