Autologous Lung Multipotent Stromal Cell Therapy for Emphysema

自体肺多能基质细胞治疗肺气肿

基本信息

批准号：
8603281
负责人：
Andrew Hoffman
金额：
$ 81.88万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-07 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8603281
关键词：
Address Adipocytes Adult Aftercare Agar Alveolar Animal Testing Animals Anoikis Autologous Autopsy Basement membrane Behavior Biocompatible Biological Assay Biopolymers Biopsy Biopsy Specimen Bone Marrow CD44 gene Cell Survival Cell Therapy Cell Transplantation Cell Transplants Cell-Matrix Junction Cells Cellular Structures Cellularity Chondrocytes Clinical Clinical Trials Design Collaborations Dana-Farber Cancer Institute Dose ENG gene Elastases Elastic Fiber Elastin Engraftment Experimental Models FGF10 gene FGF2 gene FGF7 gene Fibroblasts Growth Factor Homologous Transplantation Hour Human Hydrogels Immune response Immunosuppression In Vitro Insulin-Like Growth Factor I Integrins Interleukin-6 Label Lung Lung Transplantation Lung diseases Mechanics Mesenchymal Methods Molecular Molecular Profiling Mus Natural regeneration Organ Osteocytes Patients Perfusion Phagocytosis Pharmacology Phase Phase I Clinical Trials Physiological Procedures Production Property Pulmonary Emphysema Reporting Saline Sheep Site Staging Stem cells Stromal Cells Structure Structure of parenchyma of lung Surface Suspension substance Suspensions System Testing Tissues Toxicology Transplantation Undifferentiated Vascular Cell Adhesion Molecule-1 Work aqueous base body system cytokine design functional restoration improved in vitro Assay lung injury macrophage matrigel migration novel novel strategies pre-clinical public health relevance regenerative regenerative therapy response scaffold tissue regeneration treatment duration

项目摘要

DESCRIPTION (provided by applicant): Regenerative therapies using stem cells are being explored for treatment of advanced lung diseases such as emphysema. We recently identified an undifferentiated "fibroblast-like" multipotent stromal cell (LMSC) from lung tissue that expresses the same surface markers (CD44, CD73, CD90, CD105) as multipotent bone marrow stromal cells and displays regenerative capacity following transplantation in mice and sheep with experimental emphysema. LMSCs from adult human lung tissue have elastogenic capacity in vitro, spontaneously form alveolar-like structures in matrigel and secrete growth factors including FGF2, FGF7, FGF10, and HGF that can promote remodeling. In collaboration with the Production Assistance for Cellular Therapies (PACT) group at the Dana Farber Cancer Institute, we have developed procedures for manufacturing clinical grade LMSCs from biopsy specimens, and designed a biopolymer scaffold to promote lung engraftment of LMSCs following endobronchial administration. These technological advances make autologous LMSC transplantation feasible for human applications, addressing problems of rejection and the need for immunosuppression that are associated with allogeneic transplantation. The objectives of this project are: 1) to complete the preclinical pharmacotoxicology testing required to begin human trials. 2) Initiate Phase 1 trials of autologous LMSC transplantation in emphysema patients awaiting lung transplantation. This trial design will allow us to recover the LMSC-treated organ for histological analysis to characterize responses to LMSC treatment at the cellular level.

描述（由申请人提供）：正在探索使用干细胞再生疗法，以治疗晚期肺部疾病，例如肺气肿。我们最近从肺组织中鉴定出一种未分化的“成纤维细胞样”多能基质细胞（LMSC），该肺组织表达了相同的表面标记（CD44，CD73，CD90，CD105），作为多能骨骨髓基质细胞，并在小鼠和绵羊和绵羊中的再生能力中显示出多能的骨骨髓细胞与实验性肺气肿。来自成年人肺组织的LMSC在体外具有弹性能力，在基质中自发形成肺泡样结构，并分泌生长因子，包括FGF2，FGF7，FGF10和HGF，可以促进重塑。通过与Dana Farber癌症研究所的蜂窝疗法生产帮助（PACT）的生产帮助，我们开发了生物检查标本的临床级LMSC的程序，并设计了一个生物聚合物支架来促进内托管管理后LMSC的肺部结构。这些技术进步使自体LMSC移植可用于人类应用，解决排斥问题以及与同种异体移植有关的免疫抑制的需求。该项目的目标是：1）完成开始人类试验所需的临床前药物毒理学测试。 2）启动在等待肺移植的肺气肿患者中自体LMSC移植的试验。该试验设计将使我们能够恢复经过LMSC处理的组织学分析的器官以表征细胞水平上对LMSC治疗的反应。