Stem Cell Core B is directed by Drs. Sorrentino and Persons and provides for stem cell procurement, processing, and manipulation for both the preclinical and clinical trial procedures within this application. Dr. Persons will direct the preclinical activities in this Core which include purification and transduction of nonhuman primate cells as outlined in Project 1 as well as purification of mouse hematopoietic stem cells from murine SCD and WAS models in support of Projects 1 and 2. The Core will continue to define optimal lentiviral transduction conditions for CD34+ cells obtained from human bone marrow and G-CSF mobilized peripheral blood cells from normal volunteers. Transduction efficiencies will be determined using standard in vitro assays such as flow cytometry and CFU-C assays and also by reconstitution experiments in immunodeficient NOG mice. In addition to these preclinical and developmental functions, Core B will provide for the processing and transduction of clinical material obtained from St. Jude patients and used for the WAS clinical trial proposed in Project 2 and the LVXSCID trials in Project 3. These activities will be directed by Dr. Sorrentino. Patients treated on the LVSCID-OC trial at NIH will continue to use existing resources at the NIH clinical center under the direction of Dr. Malech and his colleagues and no funds are requested for these activities. For St. Jude patients, mobilized peripheral blood cells or bone marrow cells from patients will be collected, CD34+ cells will be obtained using a certified procedure based on the CliniMacs apparatus, cells will be transduced with certified vector supernatants prepared in our GMP facility, and processed cells will be prepared for injection into the patient. All of these clinical manipulations will be done in the St. Jude Human Applications Laboratory (HAL), which is an established clinical laboratory that supports all activities that are ongoing in the Division of Bone Marrow Transplant and Cell Therapy. Because of this expanded scope and emphasis on clinical trials, the activities and budget for the Stem Cell Core have increased from the past funding period.

Public Health Relevance

The Stem Cell Core B is relevant by providing the means for processing and transducing stem cells for use in experiments within the Program Project and also for providing genetically modified cells for use in the clinical trials within Projects 2 and 3.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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St. Jude Children's Research Hospital
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Zhao, Hui Fen; Abraham, Allistair; Kim, Yoon-Sang et al. (2017) Lentiviral Transfer of ?-Globin with Fusion Gene NUP98-HOXA10HD Expands Hematopoietic Stem Cells and Ameliorates Murine ?-Thalassemia. Mol Ther 25:593-605
De Ravin, Suk See; Wu, Xiaolin; Moir, Susan et al. (2016) Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med 8:335ra57
Abraham, Allistair; Kim, Yoon-Sang; Zhao, Huifen et al. (2016) Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2r?null Mice by Lentiviral Expression of NUP98-HOXA10HD. PLoS One 11:e0147059
Wielgosz, Matthew M; Kim, Yoon-Sang; Carney, Gael G et al. (2015) Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy. Mol Ther Methods Clin Dev 2:14063
Pestina, Tamara I; Hargrove, Phillip W; Zhao, Huifen et al. (2015) Amelioration of murine sickle cell disease by nonablative conditioning and ?-globin gene-corrected bone marrow cells. Mol Ther Methods Clin Dev 2:15045
Zhou, Sheng; Bonner, Melissa A; Wang, Yong-Dong et al. (2015) Quantitative shearing linear amplification polymerase chain reaction: an improved method for quantifying lentiviral vector insertion sites in transplanted hematopoietic cell systems. Hum Gene Ther Methods 26:4-12
Urbinati, Fabrizia; Hargrove, Phillip W; Geiger, Sabine et al. (2015) Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells. Exp Hematol 43:346-351
Treanor, Louise M; Zhou, Sheng; Janke, Laura et al. (2014) Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential. J Exp Med 211:701-13
Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2014) Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol 133:335-47
De Ravin, Suk See; Gray, John T; Throm, Robert E et al. (2014) False-positive HIV PCR test following ex vivo lentiviral gene transfer treatment of X-linked severe combined immunodeficiency vector. Mol Ther 22:244-245

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