Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, USA.
BMC Immunol. 2011 Jun 6;12:35. doi: 10.1186/1471-2172-12-35.
Dendritic cells (DCs) are antigen presenting cells capable of inducing specific immune responses against microbial infections, transplant antigens, or tumors. Interestingly, microenvironment conditions such as those present in tumor settings might induce a DC phenotype that is poorly immunogenic and with the capability of promoting angiogenesis. We hypothesize that this plasticity may be caused not only by the action of specific cytokines or growth factors but also by the properties of the surfaces with which they interact, such as extracellular matrix (ECM) components.
Herewith we studied the effect of different surfaces and soluble factors on the biology of DCs. To accomplish this, we cultured murine myeloid(m) DCs on surfaces coated with fibronectin, collagen I, gelatin, and Matrigel using poly-D-lysine and polystyrene as non-biological surfaces. Further, we cultured these cells in the presence of regular DC medium (RPMI 10% FBS) or commercially available endothelial medium (EGM-2). We determined that mDCs could be kept in culture up to 3 weeks in these conditions, but only in the presence of GM-CSF. We were able to determine that long-term DC cultures produce an array of angiogenic factors, and that some of these cultures still retain the capability to induce T cell responses.
Altogether these data indicate that in order to design DC-based vaccines or treatments focused on changing the phenotype of DCs associated with diseases such as cancer or atherosclerosis, it becomes necessary to fully investigate the microenvironment in which these cells are present or will be delivered.
树突状细胞(DCs)是一种抗原呈递细胞,能够诱导针对微生物感染、移植抗原或肿瘤的特异性免疫反应。有趣的是,肿瘤环境中的微环境条件可能会诱导出一种免疫原性差且具有促进血管生成能力的 DC 表型。我们假设这种可塑性不仅是由特定细胞因子或生长因子的作用引起的,还可能是由于它们相互作用的表面的特性引起的,例如细胞外基质(ECM)成分。
在此,我们研究了不同表面和可溶性因子对 DC 生物学的影响。为此,我们使用多聚-D-赖氨酸和聚苯乙烯作为非生物表面,在涂有纤维连接蛋白、I 型胶原、明胶和基质胶的表面上培养鼠源髓样(m)DCs。此外,我们在常规 DC 培养基(RPMI 10% FBS)或市售内皮培养基(EGM-2)中培养这些细胞。我们确定 mDCs 在这些条件下可以培养长达 3 周,但仅在 GM-CSF 存在的情况下。我们能够确定长期 DC 培养物会产生一系列血管生成因子,并且其中一些培养物仍然保留诱导 T 细胞反应的能力。
总之,这些数据表明,为了设计基于 DC 的疫苗或治疗方法,以改变与癌症或动脉粥样硬化等疾病相关的 DC 表型,有必要充分研究这些细胞存在或将要递送至的微环境。