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：
10076992
负责人：
Andrew Hoffman
金额：
$ 30.53万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10076992
关键词：
Autologous Lung Multipotent Stromal Cell

项目摘要

Project Summary/Abstract 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; and 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.

项目摘要/摘要正在探索使用干细胞再生疗法以治疗晚期肺部疾病作为肺气肿。来自表达相同表面标记（CD44，CD73，CD90，CD105）的肺组织骨髓基质细胞并显示在小鼠和绵羊中移植后的再生Capace。实验性肺气肿。自发形成肺泡状结构，并分泌生长因子，包括FGF2，FGF7，FGF7， FGF10和HGF可以促进重塑。 Dana Farber癌症研究所的疗法（PACT）组，我们已经开发了程序从活检标本制造进化枝级LMSC，并设计了一个生物聚合物支架来促进肺部的LMSC肺部管理后的肺部。自体LMSC移植可用于人类应用，解决拒绝问题和您与同种异体移植相关的Imunosepression的需求。是：1）汇编开始人类试验所需的临床前药物学测试；肺气肿患者的自体LMSC移植的1阶段试验试验设计将使我们能够恢复LMSC处理的器官进行组织学分析，以表征反应在细胞水平上进行LMSC治疗。