Mesenchymal stem cell enhancement of organ allograft repair and long term surviva

间充质干细胞增强器官同种异体移植修复和长期存活

• 批准号: 8514489
• 负责人: Amelia M. Bartholomew
• 金额: $ 77.62万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 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/8514489
• 关键词: Allografting; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Aspirate substance; Autoimmune Diseases; Autologous; Bioinformatics; Biological Markers; Biopsy; Bone Marrow; Clinical Trials; Collaborations; Cytokine Suppression; Data; Data Analyses; Data Set; Dendritic Cells; Development; Diabetes Mellitus; Dialysis procedure; Dose; Event; Experimental Models; Fibrosis; Frequencies; Genomics; Goals; Growth Factor; Heart Transplantation; Human; Hypertension; Immune response; Immunosuppression; Immunosuppressive Agents; Infiltration; Inflammatory; Injury; Instruction; Interferon Type II; Interleukin-10; Interleukin-2; Ischemia; Kidney Failure; Kidney Transplantation; Macaca fascicularis; Machine Learning; Mesenchymal Stem Cells; Modeling; Mus; Musculoskeletal; Natural regeneration; Necrosis; Obesity; Organ Transplantation; Outcome; Outcome Measure; Papio; Population; Predictive Value; Preparation; Prevalence; Production; Property; Protocols documentation; Regimen; Relative (related person); Reperfusion Injury; Reporting; Reproducibility; Sample Size; Sampling; Schedule; Signal Transduction; Skin; Source; T cell regulation; T-Lymphocyte; Testing; The Sun; Therapeutic; Time; TimeLine; Tissues; Transforming Growth Factor beta; Transplantation; Vascular Endothelial Growth Factors; bone morphogenetic protein 7; clinical application; comparative efficacy; design; efficacy testing; functional outcomes; graft vs host disease; improved; islet; islet allograft; kidney allograft; monocyte; neutrophil; nonhuman primate; novel; pandemic disease; peripheral blood; pre-clinical; predictive modeling; prevent; primary outcome; progenitor; programs; regenerative; repaired; response; secondary outcome; statistics; symposium; tumor

PROJECT SUMMARY (See Instructions): Mesenchymal stem cells (MSC), expanded from bone marrow aspirates, have demonstrated immunosuppressive and regenerative properties in animal models. While human clinical trials have been initiated in graft versus host disease, autoimmune disorders, and musculoskeletal regeneration, application to transplants has lagged behind. Murine and pre-clinical experimental models have raised specific concerns of allo-sensitization, reproducibility of MSC phenotypic and functional characterization, and optimal indication post-transplant. In this Project 2 of the Program, efficacy studies will be undertaken to define optimize immunosuppressive and regenerative functions of MSC. In aim 1, we will test whether interferon gamma activated MSC provide greater homogeneity in form and function when compared to non-activated MSC and we will define the relative contribution of MHC matched MSC to mismatched ones on renal allograft function in the setting of a sub-therapeutic immunosuppressive regimen. We will test the efficacy of MSC in reducing tissue injury from prolonged cold ischemia times in Aim 2 and in Aim 3, through the collaboration with Cores B and C, the secondary outcome measures which include longitudinal assessments of immune responses, tissue biopsies, and endothelial progenitor frequencies will be correlated to the primary outcome measure, 100-day rejection free survival, to define efficacy. Assessments will be undertaken proteomically and genomically via Core B and then compiled and statistically analyzed in Core C using both classical statistics and a novel machine learning approach which has the potential to maximize data analysis from small sample sizes. These efficacy studies will be undertaken in a pre-clinical renal transplant model to parallel similar studies in a pre-clinical islet model in Project 1. Synergy between this project, Project 1, and Cores B and C will be facilitated by the Administrative Core, which will coordinate monthly conference calls, track samples to the Cores, and follow the progress on timelines and deliverables. These studies support our long-term goal, which is to demonstrate MSC efficacy or non-efficacy in minimizing baseline immunosuppression.

项目概述（见项目说明）：