A 3-dimensional extracellular matrix as a delivery system for the transplantation of glioma-targeting neural stem/progenitor cells
A 3-dimensional extracellular matrix as a delivery system for the transplantation of glioma-targeting neural stem/progenitor cells
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DOI：
10.1093/neuonc/noq002
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发表时间：
2010-07-01
期刊：
影响因子：
15.9
通讯作者：
Schmidt, Nils Ole
中科院分区：
文献类型：
--
作者：
Hansen, Katharina;Mueller, Franz-Josef;Schmidt, Nils Ole
神经干/祖细胞（NSPCs）显示出固有的致病特性，可用于靶向递送治疗基因，以治疗中枢神经系统中的侵袭性恶性肿瘤。优化移植效率对于开发相关的基于NSPC的脑肿瘤疗法至关重要。迄今为止，在神经外科切除腔的背景下处理和固定NSPC的现实问题尚未得到解决。使用生物相容性装置的干细胞移植是一种有前途的方法，以抵消不良的NSPC移植物存活和整合在各种类型的神经系统疾病。在这里，我们报告了一个三维基板，是基于细胞外基质纯化的组织工程皮肤培养（3DECM）的发展。3DECM能够在体外扩增包埋的NSPCs，同时保持其未定型的分化状态。当植入脑内胶质瘤模型时，NSPC能够从3DECM迁移到对侧半球生长的靶向胶质瘤，这比通过脑内注射细胞悬液递送NSPC更有效。将3DECM植入物直接应用于肿瘤切除腔导致复发性胶质瘤的显著NSPC浸润。3DECM植入物的半固体一致性允许在脑内和腔内应用的外科手术过程中进行简单处理，并确保与周围脑实质的持续接触。在这里，我们展示了基质支持的肿瘤靶向NSPC移植的概念验证。作为NSPC的递送系统的半固体3DECM具有通过减少代谢应激和提供机械支持来提高移植效率的潜力，特别是当在脑肿瘤切除后施用至手术切除腔时。
Neural stem/progenitor cells (NSPCs) display inherent pathotropic properties that can be exploited for targeted delivery of therapeutic genes to invasive malignancies in the central nervous system. Optimizing transplantation efficiency will be essential for developing relevant NSPC-based brain tumor therapies. To date, the real-world issue of handling and affixing NSPCs in the context of the neurosurgical resection cavity has not been addressed. Stem cell transplantation using biocompatible devices is a promising approach to counteract poor NSPC graft survival and integration in various types of neurological disorders. Here, we report the development of a 3-dimensional substrate that is based on extracellular matrix purified from tissue-engineered skin cultures (3DECM). 3DECM enables the expansion of embedded NSPCs in vitro while retaining their uncommitted differentiation status. When implanted in intracerebral glioma models, NSPCs were able to migrate out of the 3DECM to targeted glioma growing in the contralateral hemisphere, and this was more efficient than the delivery of NSPC by intracerebral injection of cell suspensions. Direct application of a 3DECM implant into a tumor resection cavity led to a marked NSPC infiltration of recurrent glioma. The semisolid consistency of the 3DECM implants allowed simple handling during the surgical procedure of intracerebral and intracavitary application and ensured continuous contact with the surrounding brain parenchyma. Here, we demonstrate proof-of-concept of a matrix-supported transplantation of tumor-targeting NSPC. The semisolid 3DECM as a delivery system for NSPC has the potential to increase transplantation efficiency by reducing metabolic stress and providing mechanical support, especially when administered to the surgical resection cavity after brain tumor removal.