Center for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, 46022 Valencia, Spain.
Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 46022 Valencia, Spain.
Int J Mol Sci. 2020 Aug 11;21(16):5747. doi: 10.3390/ijms21165747.
In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.
在血液系统恶性肿瘤（如白血病或骨髓瘤）中，恶性细胞具有骨髓归巢的特性，骨髓龛在肿瘤的发生和耐药中起着重要作用。骨髓的结构、细胞和分子组成以及相互作用决定了不同的微环境，这些微环境在生理和病理条件下控制着细胞的命运，并为试图复制血液癌症行为的工程化平台提供了参考，以重现其固有生物学特征。本综述总结了用于在体外有效再现骨髓某些方面的不同模型；然而，它们仍然缺乏该组织的复杂性，这对于诸如多发性骨髓瘤中耐药性发展等基本方面非常重要。细胞外基质组成、材料拓扑结构、血管化、细胞组成或干性与分化平衡等变量可在组织工程方法中进行合理定义，以实现更相关的体外模型。完全人源化的平台与天然相互作用非常相似，但仍具有挑战性，关于在多大程度上准确复制组织复杂性对于可靠预测药物反应至关重要的问题存在争议。然而，这些方法对非实体瘤生物学的基础认识、龛在其调控中的作用以及个性化医疗的发展都具有重要意义。
