NIDCR Contribution to NIH Bone Marrow Stromal Cell Transplantation Center

NIDCR 对 NIH 骨髓基质细胞移植中心的贡献

• 批准号: 8743783
• 负责人: PAMELA G ROBEY
• 金额: $ 12.25万
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8743783
• 关键词: Acute Graft Versus Host Disease; Adipocytes; Aging; Aging-Related Process; Allogenic; Autologous; Biological; Bone Marrow; Bone Regeneration; Bone necrosis; Cartilage; Cell Aging; Cell Differentiation process; Cell Transplantation; Cells; Clinical; Clinical Investigator; Clinical Protocols; Collection; Coronary Artery Bypass; Data; Depressed mood; Disease; FDA approved; Failure; Freezing; Funding; Future; Genes; Growth Factor; Hematopoiesis; Human; Immunosuppressive Agents; In Vitro; Inflammatory Bowel Diseases; Infusion procedures; Injection of therapeutic agent; Injury; Institutes; Institutional Review Boards; Jaw; Lasers; Lead; Leadership; Left Ventricular Function; Marrow; Methods; Microarray Analysis; Mission; Molecular Profiling; Monitor; Myocardial; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Biomedical Imaging and Bioengineering; National Institute of Dental and Craniofacial Research; National Institute of Neurological Disorders and Stroke; Nature; Patients; Pharmaceutical Preparations; Population; Preparation; Process; Production; Protocols documentation; Qualifying; Safety; Staging; Stem cell transplant; Stem cells; Stromal Cells; Techniques; Tissue Engineering; Tissues; United States National Institutes of Health; animal model development; base; bone; cell age; citrin; cranium; cytokine; follow-up; healthy volunteer; improved; open label; paracrine; phase 1 study; repaired; response; skeletal; stem; transcriptomics

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.

在过去的一年中，BMSCTC有许多活动。 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同种异体干细胞移植后，Battiwalla和Barrett，NHLBI，PIS的骨髓基质细胞输注，治疗急性移植物与宿主疾病，骨髓衰竭和组织损伤。 该试验正在随访中，数据正在分析中。 同种异体细胞也用于治疗炎症性肠病（13-I-i-0077-一项开放标签的1阶段研究，以评估骨髓骨髓基质细胞输注的安全性和耐受性，用于治疗中度至重度炎性肠道疾病，YAO，YAO，NIAID，PI），刚刚开始患者。 在冠状动脉旁路和跨心肌激光血管血管化下，生成自体细胞在患者中直接使用（无冻结）（12 h-0078-第12 h-0078-初步评估直接评估自体内注射自体内的自体内注射自体骨髓骨髓细胞的骨膜细胞，该细胞受到毛刺的血管生长，伴随着毛细血管的伴随着毛皮，剩下的Pi and rob，左rob，左rob，左甲状腺肿，左rob，耐皮因素，左rob，左型螺旋形， NHLBI，LAI）。 处理颌骨骨坏死的另外两种临床方案（Shastry和Robey，Nidcr； Citrin和Landgren，NCI）和颅骨再生（Robey，NIDCR）正在准备。 除了准备临床级BMSC外，该中心还在开发技术以更好地监测其在体内扩张期间的生物学活性。 这种监测将提高在临床使用之前鉴定特定细胞的资格的能力。 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签名，可以确定对改善的患者进行的批次中存在的因素，而这些因素与对未改善的患者进行的患者相比。 此外，通过研究不同阶段的不同供体的细胞的谱，如果体外衰老，似乎有24个基因（12个被上调的基因和十二个被下调的基因）似乎可以预测细胞的年龄。 还发现体外衰老过程中存在供体变异性（即，一些段落5处的供体细胞的签名与从第10通道10的另一个供体的签名类似）。 这24个基因的列表可能在确定中心开发的未来细胞批次的释放标准中很有用。