Abstract

Hematopoietic stem cells reside within the bone marrow post-natally, providing all hematopoietic lineages for the life of the host, and their extensive characterization over the last several decades has led to clinical application including bone marrow transplantation for benign and malignant disorders affecting the hematopoietic compartment. Isolation of bone marrow cells based upon expression of the CD34 antigen enriches for the primitive compartment, and techniques to isolate the CD34-positive population are commonly used in clinical practice. Assays for true hematopoietic stem cells require transplantation and repopulation, and thus studies querying such potential among human cells are difficult. We have thus developed a xenograft model with robust human hematopoietic stem cell engraftment, and have demonstrated engraftment of all cell lineages. This assay will allow us to test globin vectors for the first time among engrafted human cells in a relevant model.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006009-07
Application #
8939815
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Leonard, Alexis; Tisdale, John F (2018) Stem cell transplantation in sickle cell disease: therapeutic potential and challenges faced. Expert Rev Hematol 11:547-565
Uchida, Naoya; Haro-Mora, Juan J; Fujita, Atsushi et al. (2017) Efficient Generation of ?-Globin-Expressing Erythroid Cells Using Stromal Cell-Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease. Stem Cells 35:586-596
Uchida, Naoya; Fujita, Atsushi; Hsieh, Matthew M et al. (2017) Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell Disease: Evidence from Rhesus and SCD Patients. Hum Gene Ther Clin Dev :
Fujita, Atsushi; Uchida, Naoya; Haro-Mora, Juan J et al. (2016) ?-Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs. Stem Cells 34:1541-52
Uchida, Naoya; Green, Rashidah; Ballantine, Josiah et al. (2016) Kinetics of lentiviral vector transduction in human CD34(+) cells. Exp Hematol 44:106-15
Evans, Molly E; Kumkhaek, Chutima; Hsieh, Matthew M et al. (2014) TRIM5? variations influence transduction efficiency with lentiviral vectors in both human and rhesus CD34(+) cells in vitro and in vivo. Mol Ther 22:348-58
Kovtunovych, Gennadiy; Ghosh, Manik C; Ollivierre, Wade et al. (2014) Wild-type macrophages reverse disease in heme oxygenase 1-deficient mice. Blood 124:1522-30
Herman, S E M; Sun, X; McAuley, E M et al. (2013) Modeling tumor-host interactions of chronic lymphocytic leukemia in xenografted mice to study tumor biology and evaluate targeted therapy. Leukemia 27:2311-21
Kumkhaek, Chutima; Aerbajinai, Wulin; Liu, Wenli et al. (2013) MASL1 induces erythroid differentiation in human erythropoietin-dependent CD34+ cells through the Raf/MEK/ERK pathway. Blood 121:3216-27
Perl, Shira; Perlman, Jordan; Weitzel, R P et al. (2013) Addition of rapamycin to anti-CD3 antibody improves long-term glycaemia control in diabetic NOD mice. PLoS One 8:e67189

Showing the most recent 10 out of 21 publications