Functionalized 3D scaffolds for engineering the hematopoietic niche.
Functionalized 3D scaffolds for engineering the hematopoietic niche.
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DOI：
10.3389/fbioe.2022.968086
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发表时间：
2022
影响因子：
5.7
通讯作者：
Fraternale, Alessandra
中科院分区：
文献类型：
--
作者：
Bruschi, Michela;Vanzolini, Tania;Sahu, Neety;Balduini, Alessandra;Magnani, Mauro;Fraternale, Alessandra
造血干细胞（HSC）位于骨髓（BM）的亚区中，该亚区被定义为造血生态位，在那里，通过分化和自我更新的相互作用，它们可以产生免疫细胞和血细胞。人工造血生态位首先在2D体外培养中开发，但有限的扩增潜力和干性维持诱导这些系统的优化，以避免天然组织复杂性的完全丧失。接下来的步骤是通过工程设计不同的材料，如水凝胶，天然或合成聚合物的纤维结构，陶瓷等，以生产更类似BM的3D基底。细胞因子、可溶性因子、粘附分子、细胞外基质（ECM）成分和其他小生境驻留细胞的分泌组在控制和调节HSC定型中发挥重要作用。为了提供生化线索，利用共培养物和饲养层以及天然或合成分子。这篇综述收集了用于3D支架功能化的关键要素，这些要素被证明可以促进HSC的生长和分化，包括1）生物物理学线索，即，材料、形貌、硬度、氧张力和流体剪切应力到2）ECM元件、饲养细胞层和氧化还原清除剂的存在有利于生物化学暗示。特别关注的是3D系统，以重建巨核细胞产品，应用于血细胞生产，而HSC在这种3D结构的临床应用是有限的，到目前为止，BM疾病的测试。
Hematopoietic stem cells (HSCs) reside in a subzone of the bone marrow (BM) defined as the hematopoietic niche where, via the interplay of differentiation and self-renewal, they can give rise to immune and blood cells. Artificial hematopoietic niches were firstly developed in 2D in vitro cultures but the limited expansion potential and stemness maintenance induced the optimization of these systems to avoid the total loss of the natural tissue complexity. The next steps were adopted by engineering different materials such as hydrogels, fibrous structures with natural or synthetic polymers, ceramics, etc. to produce a 3D substrate better resembling that of BM. Cytokines, soluble factors, adhesion molecules, extracellular matrix (ECM) components, and the secretome of other niche-resident cells play a fundamental role in controlling and regulating HSC commitment. To provide biochemical cues, co-cultures, and feeder-layers, as well as natural or synthetic molecules were utilized. This review gathers key elements employed for the functionalization of a 3D scaffold that demonstrated to promote HSC growth and differentiation ranging from 1) biophysical cues, i.e., material, topography, stiffness, oxygen tension, and fluid shear stress to 2) biochemical hints favored by the presence of ECM elements, feeder cell layers, and redox scavengers. Particular focus is given to the 3D systems to recreate megakaryocyte products, to be applied for blood cell production, whereas HSC clinical application in such 3D constructs was limited so far to BM diseases testing.
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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