Artificial, Humanized Stem Cell Niches

描述(申请人提供)：该项目的总体目标是优化和部署一种生物工程植入物，以增加骨髓衰竭状态下移植的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)设计临床使用种植体抢救骨髓衰竭的方案；(3)影像引导下的种植体治疗监测。我们的预期贡献是开发一种新的生物工程骨髓贴片，这一点意义重大，因为这里开发的方案可以通过提高骨髓移植的效率来拯救数千名死于骨髓衰竭的患者。 与公共健康相关：我们已经开发出了基质细胞负载的3D微制生物材料(称为贴片)，它模拟了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，作为一种在骨髓衰竭时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.