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。我们最近确定了一个未分化的“成纤维细胞样”多能基质细胞（LMSC）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在小鼠和绵羊移植后显示再生能力实验性肺气肿。来自成人人类肺组织的LMSC在体外具有弹性能力，赞助在基质中形成牙槽样结构。以及包括FGF2，FGF7在内的秘密增长因素， FGF10和HGF可以促进重塑。与蜂窝的生产协助合作 Dana Farber癌症研究所的疗法（PACT）组，我们已经开发了程序制造活检标本的临床级LMSC，并设计了一个生物聚合物支架来促进支撑器给药后LMSC的肺植入。这些技术进步使自体LMSC移植可用于人类应用，解决拒绝问题和与同种异体移植有关的免疫抑制的需求。这个项目的目标是：1）完成开始人类试验所需的临床前药物毒理学测试； 2）发起在等待肺移植的肺气肿患者中自体LMSC移植的1阶段试验。这试验设计将使我们能够恢复经过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。