Autologous Lung Multipotent Stromal Cell Therapy for Emphysema

自体肺多能基质细胞治疗肺气肿

• 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
• 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

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.

项目概要/摘要 正在探索使用干细胞的再生疗法来治疗晚期肺部疾病，例如 我们最近发现了一种未分化的“成纤维细胞样”多能基质细胞（LMSC）。 来自表达与多能骨相同的表面标志物（CD44、CD73、CD90、CD105）的肺组织 骨髓基质细胞移植到小鼠和绵羊体内后显示出再生能力 来自成人肺组织的实验性肺气肿细胞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生长因子，包括 FGF2、FGF7、 与细胞生产援助合作，可促进重塑的 FGF10 和 HGF。 达纳法伯癌症研究所的治疗 (PACT) 小组，我们开发了以下程序： 利用活检标本制造临床级 LMSC，并设计了生物聚合物支架以促进 这些技术进步使得支气管内给药后 LMSC 的肺移植成为可能。 自体 LMSC 移植可用于人体，解决排斥问题和 与同种异体移植相关的免疫抑制的需求。 是：1) 完成开始人体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进行自体 LMSC 移植的 1 期试验。 试验设计将使我们能够恢复经 LMSC 处理的器官进行组织学分析，以表征反应 细胞水平的 LMSC 治疗。

项目成果

Lung regeneration and translational implications of the postpneumonectomy model.

肺切除术后模型的肺再生和转化意义。

• DOI: 10.1016/j.trsl.2013.11.010
• 发表时间: 2014-04-01
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: K. Thane;E. Ingenito;A. Hoffman
• 通讯作者: A. Hoffman

Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration.

肺再生过程中细支气管肺泡干细胞反应的细胞动力学和建模。

• DOI: 10.1152/ajplung.00298.2007
• 发表时间: 2008-06-01
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: R. Nolen;Carla F. Kim;M. Mazan;E. Ingenito;A. Gruntman;L. Tsai;R. Boston;Amber Woolfenden;T. Jacks;A. Hoffman
• 通讯作者: A. Hoffman