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采集方案（10-CC-0053-采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），已经建立了一个冷冻BMSC库，用于治疗急性移植物抗宿主病的临床方案中的同种异体使用（12-H-0010-骨髓基质细胞输注治疗同种异体干细胞移植后急性移植物抗宿主病、骨髓衰竭和组织损伤的I期研究，Battiwalla和Barrett，NHLBI，PI）。 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-0077-一项评估骨髓基质细胞输注治疗中度至重度炎症性肠病的安全性和耐受性的开放标签、I期研究，Yao，NIAID，PI），该试验刚刚开始招募患者。 生成自体骨髓基质细胞，直接用于（不冷冻）进行冠状动脉旁路移植术和经心肌激光血运重建的患者（12-H-0078-对患有左心室功能抑制的CAD患者进行血运重建的自体骨髓基质细胞直接心肌内注射的初步评估，Robey，NIDCR，PI和Horvath，NHLBI，LAI）。 另外两个治疗颌骨骨坏死（Shastry和Robey，NIDCR; Citrin和Landgren，NCI）和颅骨再生（Robey，NIDCR）的临床方案正在准备中。 除了制备临床级BMSC外，该中心还开发了在体外扩增过程中更好地监测其生物活性的技术。 这种监测将提高在临床使用之前鉴定特定批次细胞的能力。 每个细胞批次都进行分子分析（微阵列分析和其他方法）。 通过具有特定批次的转录组学特征，可以确定存在于给予改善的患者的批次中的因子与给予未改善的患者的批次中的因子。 此外，通过研究来自不同供体的细胞在体外老化的不同阶段的特征，24个基因（12个上调，12个下调）的列表似乎可以预测细胞的年龄。 还发现在体外老化过程中存在供体可变性（即，第5代的一些供体细胞具有与第10代的另一供体细胞相似的标记。 这24个基因的列表可能有助于确定该中心开发的未来细胞批次的放行标准。

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.