Department Medical Biotechnology, Technische Universität Berlin, Institute of Biotechnology, Berlin, Germany.
Berlin-Brandenburg School for Regenerative Therapies, Charitè Campus Virchow Klinikum, Berlin, Germany.
J Tissue Eng Regen Med. 2018 Feb;12(2):479-489. doi: 10.1002/term.2507. Epub 2017 Nov 5.
Multipotent haematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to date, no in vitro model exists that accurately mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, a novel three-dimensional coculture model is presented, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic multiorgan chip. The HSPCs were found to stay in their primitive state (CD34 CD38 ) and capable of granulocyte, erythrocyte, macrophage, megakaryocyte colony formation. Furthermore, a microenvironment was formed bearing molecular and structural similarity to the in vivo bone marrow niche containing extracellular matrix and signalling molecules known to play an important role in HSPC homeostasis. Here, a novel human in vitro bone marrow model is presented for the first time, capable of long-term culture of primitive HSPCs in a microfluidic environment.
多能造血干细胞和祖细胞（HSPCs）是所有血细胞类型的来源。已知 HSPCs 所在的骨髓干细胞龛对于其维持是至关重要的。不幸的是，迄今为止，尚无体外模型能够准确模拟骨髓龛的各个方面，同时又能长期培养 HSPCs。在这项研究中，提出了一种基于涂有羟基磷灰石的氧化锆支架的新型三维共培养模型，其中包含人基质基质细胞（MSCs）和脐血来源的 HSPCs，使 HSPCs 能够在微流控多器官芯片中成功培养 28 天。发现 HSPCs 保持原始状态（CD34 CD38），并且能够形成粒细胞、红细胞、巨噬细胞、巨核细胞集落。此外，形成了一种具有与体内骨髓龛相似的分子和结构的微环境，其中包含已知在 HSPC 动态平衡中起重要作用的细胞外基质和信号分子。这里，首次提出了一种新型的人类体外骨髓模型，能够在微流控环境中长期培养原始 HSPCs。
