Stem Cell Core

干细胞核心B由Sorrentino博士和Persons博士指导，并提供干细胞采购， 本申请中的临床前和临床试验程序的处理和操作。博士 人员将指导本核心的临床前活动，包括非人源性细胞的纯化和转导。 项目1中概述的灵长类细胞以及从小鼠造血干细胞中纯化造血干细胞。 小鼠SCD和WAS模型，以支持项目1和2。核心将继续定义最佳 从人骨髓获得的CD 34+细胞和G-CSF动员的慢病毒转导条件 正常志愿者的外周血细胞。转换效率将使用标准的 体外测定，如流式细胞术和CFU-C测定，也可以通过重组实验， 免疫缺陷NOG小鼠。除了这些临床前和开发功能外，核心B还将提供 用于处理和转换从St. Jude患者获得并用于WAS的临床材料 项目2中拟定的临床试验和项目3中的LVXSCID试验。这些活动将由博士指导。 Sorrentino在NIH进行LVSCID-OC试验的患者将继续使用NIH的现有资源 Malech博士及其同事指导下的临床中心，不要求这些资金 活动对于St. Jude患者，将从患者中动员外周血细胞或骨髓细胞， 将使用基于CliniMacs仪器、细胞和/或细胞的认证程序获得收集的CD 34+细胞。 将用在我们的GMP设施中制备的经认证的载体上清液进行转导， 准备注射到病人体内。所有这些临床操作都将在圣犹达人 应用实验室（HAL），这是一个成熟的临床实验室，支持所有活动， 骨髓移植和细胞治疗部正在进行。由于这种扩大的范围和 强调临床试验，干细胞核心的活动和预算比过去增加了 融资期。

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.