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的再生疗法来治疗肺气肿等晚期肺部疾病。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），其表达与多能骨髓基质细胞相同的表面标记（CD44、CD73、CD90、CD105），并在小鼠和绵羊移植后显示出再生能力患有实验性肺气肿。来自成人肺组织的 LMSCs 在体外具有弹性生成能力，在基质胶中自发形成肺泡样结构，并分泌可促进重塑的生长因子，包括 FGF2、FGF7、FGF10 和 HGF。我们与达纳法伯癌症研究所的细胞治疗生产援助 (PACT) 小组合作，开发了从活检标本中制造临床级 LMSC 的程序，并设计了一种生物聚合物支架，以促进支气管内给药后 LMSC 的肺移植。这些技术进步使得自体 LMSC 移植可用于人类，解决与同种异体移植相关的排斥问题和免疫抑制需求。该项目的目标是：1）完成开始人体试验所需的临床前药物毒理学测试。 2）在等待肺移植的肺气肿患者中启动自体LMSC移植的1期试验。该试验设计将使我们能够恢复经 LMSC 处理的用于组织学分析的器官，以在细胞水平上表征对 LMSC 治疗的反应。