Baumgartner Johanna, Jönsson Jan-Ingvar, Jager Edwin W H
Department of Physics, Chemistry and Biology (IFM), 581 83 Linköping, Sweden.
J Mater Chem B. 2018 Jul 28;6(28):4665-4675. doi: 10.1039/c8tb00782a. Epub 2018 Jul 2.
Hematopoietic stem cells are used in transplantations for patients with hematologic malignancies. Scarce sources require efficient strategies of expansion, including polymeric biomaterials mimicking architectures of bone marrow tissue. Tissue microenvironment and mode of cytokine presentation strongly influence cell fate. Although several cytokines with different functions as soluble or membrane-bound mediators have already been identified, their precise roles have not yet been clarified. A need exists for in vitro systems that mimic the in vivo situation to enable such studies. One way is to establish surfaces mimicking physiological presentation using protein-immobilization onto polymer films. However these films merely provide a static presentation of the immobilized proteins. It would be advantageous to also dynamically change protein presentation and functionality to better reflect the in vivo conditions. The electroactive polymer polypyrrole shows excellent biocompatibility and electrochemically alters its surface properties, becoming an interesting choice for such setups. Here, we present an in vitro system for switchable presentation of membrane-bound cytokines. We use interleukin IL-3, known to affect hematopoiesis, and show that when immobilized on polypyrrole films, IL-3 is bioavailable for the bone marrow-derived FDC-P1 progenitor cell line. Moreover, IL-3 presentation can be successfully altered by changing the redox state of the film, in turn influencing FDC-P1 cell viability. This novel in vitro system provides a valuable tool for stimuli-responsive switchable protein presentation allowing the dissection of relevant mediators in stem and progenitor cell behavior.
造血干细胞用于血液系统恶性肿瘤患者的移植治疗。来源稀缺需要高效的扩增策略，包括模仿骨髓组织结构的聚合生物材料。组织微环境和细胞因子的呈现方式强烈影响细胞命运。尽管已经鉴定出几种具有不同功能的细胞因子，可作为可溶性或膜结合介质，但它们的确切作用尚未阐明。需要体外系统来模拟体内情况以进行此类研究。一种方法是通过将蛋白质固定在聚合物膜上来建立模仿生理呈现的表面。然而，这些膜仅仅提供了固定化蛋白质的静态呈现。动态改变蛋白质的呈现和功能以更好地反映体内条件将是有利的。电活性聚合物聚吡咯具有出色的生物相容性，并能通过电化学方式改变其表面性质，成为此类设置的一个有趣选择。在此，我们展示了一种用于膜结合细胞因子可切换呈现的体外系统。我们使用已知会影响造血作用的白细胞介素IL-3，并表明当固定在聚吡咯膜上时，IL-3对源自骨髓的FDC-P1祖细胞系具有生物活性。此外，通过改变膜的氧化还原状态可以成功改变IL-3的呈现，进而影响FDC-P1细胞的活力。这种新型体外系统为刺激响应性可切换蛋白质呈现提供了一种有价值的工具，有助于剖析干细胞和祖细胞行为中的相关介质。
