NIDCR Contribution to NIH Bone Marrow Stromal Cell Transplantation Center

在过去一年中，BMSCTC开展了一些活动。使用中心批准的骨髓获取方案（10-CC-0053 -收集健康志愿者和患者的骨髓用于生产临床骨髓基质细胞（BMSC）产品，Stroncek， CC， PI），冷冻骨髓干细胞库已经建立，用于治疗急性移植物抗宿主病的临床方案（12-H-0010 -骨髓基质细胞输注治疗急性移植物抗宿主病的I期研究）。同种异体干细胞移植后的骨髓衰竭和组织损伤，Battiwalla和Barrett， NHLBI, PIs)。该试验正在随访中，数据正在分析中。同种异体细胞也被用于治疗炎症性肠病的试验（13-I-0077 -一项开放标签的i期研究，评估骨髓基质细胞输注治疗中重度炎症性肠病的安全性和耐受性，Yao， NIAID， PI），该试验刚刚开始患者累积。在冠状动脉旁路移植术和经心肌激光血运重建术患者中直接使用自体细胞（不冷冻）（12-H-0078 -心肌内直接注射自体骨髓基质细胞对冠心病左心室功能下降患者血运重建术的初步评估，Robey， NIDCR， PI和Horvath， NHLBI， LAI）。另外两个治疗颌骨骨坏死的临床方案（Shastry和Robey， NIDCR； Citrin和Landgren， NCI）和颅骨再生（Robey， NIDCR）正在准备中。

There have been a number of activities in the BMSCTC during the past year. Using the Centers approved bone marrow acquisition protocol (10-CC-0053 - Collection of Bone Marrow from Healthy Volunteers and Patients for the Production of Clinical Bone Marrow Stromal Cell (BMSC) Products, Stroncek, CC, PI), a bank of frozen BMSCs has been established for allogeneic use in a clinical protocol for the treatment of acute Graft Versus Host Disease (12-H-0010 - A Phase I Study of Bone Marrow Stromal Cell Infusions to Treat Acute Graft Versus Host Disease, Marrow Failure and Tissue Injury After Allogeneic Stem Cell Transplantation, Battiwalla and Barrett, NHLBI, PIs). This trial is in follow-up and data are under analysis. The allogeneic cells are also being used in a trial to treat inflammatory bowel disease (13-I-0077 - An Open-Label, Phase 1 Study to Assess the Safety and Tolerability of Bone Marrow Stromal Cell Infusion for the treatment of Moderate to Severe Inflammatory Bowel Disease, Yao, NIAID, PI), which has just started patient accrual. Autologous cells were generated for direct use (no freezing) in patients under going coronary artery bypass grafting and trans myocardial laser revascularization (12-H-0078 - Preliminary Assessment of Direct Intra-Myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for CAD with Depressed Left Ventricular Function, Robey, NIDCR, PI and Horvath, NHLBI, LAI). Two other clinical protocols for the treatment of osteonecrosis of the jaw (Shastry and Robey, NIDCR; Citrin and Landgren, NCI), and skull bone regeneration (Robey, NIDCR) are under preparation. In addition to preparing clinical grade BMSCs, the Center also has been developing techniques to better monitor their biological activity during ex vivo expansion. Such monitoring will improve the ability to qualify a particular lot of cells prior to their clinical use. Every cell lot under goes molecular profiling (microarray analysis and other methods). By having the transcriptomic signature of a particular lot, it may be possible to determine factors that were present in lots that were administered to patients that improved versus those that were administered to patients that did not improve. In addition, by studying the profile of the cells from different donors at different stages if in vitro aging, a list of 24 genes (12 that were up-regulated and twelve that were down-regulated) appeared to predict the age of the cells. It was also found that there is donor variability in the in vitro aging process (i.e., some donors cells at passage 5 had a similar signature as those from another donor at passage 10). This list of 24 genes may be useful in determining release criteria of future cell lots developed by the center.