Artificial, Humanized Stem Cell Niches

描述（由申请人提供）：本项目的总体目标是优化和部署生物工程植入物，以增加骨髓衰竭状态下移植造血干细胞的表观空间。该项目的具体目标是：（1）确定植入物的关键制造参数。(2)设计使用植入物挽救骨髓衰竭的临床方案;（3）植入物治疗的图像引导监测。我们的预期贡献是开发一种新的生物工程骨髓补片，这是重要的，因为这里开发的协议可以通过使骨髓移植更有效来挽救数千名死于骨髓衰竭的患者。 公共卫生相关性：我们已经开发了基质细胞负载的3D微制造生物材料（称为补丁），模仿骨髓的造血诱导微环境。我们现在计划评估这些补片的植入，作为在骨髓衰竭期间增加造血干细胞植入的有效空间的方法。贴片疗法的创建、治疗测试和监测被提议将临床前研究转化为人体试验。

DESCRIPTION (provided by applicant): The overall goal of this project is to optimize and deploy a bioengineered implant to increase the apparent space for transplanted hematopoietic stem cells during states of marrow failure. The project specific aims are: (1) Identify critical manufacturing parameters of the implant. (2) Design a clinical protocol for use of implants to rescue bone marrow failure, and (3) Image-guided monitoring of the implant therapy. Our expected contribution is the development of a novel bioengineered bone marrow patch that is significant because the protocols developed here could rescue thousands of patients who die from marrow failure by making marrow transplantation more efficient. PUBLIC HEALTH RELEVANCE: We have developed stromal cell-laden 3D microfabricated biomaterials (referred to as patches) that mimic the hematopoietic inductive microenvironment of the bone marrow. We now plan to evaluate the implantation of these patches as an approach to increase the effective space for hematopoietic stem cell engraftment during marrow failure. The creation, therapeutic testing, and monitoring of patch therapy is proposed to translate pre-clinical studies towards human trials.