Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia; Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074 Wuerzburg, Germany.
Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia; George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive Northwest, Atlanta, GA 30332, USA; Institute for Advanced Study, Technical University Munich, Lichtenbergstraße 2a, 85748 Garching, Munich, Germany.
Biomaterials. 2015 Aug;61:103-14. doi: 10.1016/j.biomaterials.2015.04.057. Epub 2015 May 19.
Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.
组织工程学的进步为专门设计适合造血干细胞 (HSCs) 的微环境提供了多功能工具盒，以便研究在这种环境下发展的疾病。然而，大多数当前的体内模型都无法再现人类体内的生物学过程。在这里，我们描述了一种高度可重现的方法，用于构建能够再现 HSC 龛位形态特征和生物学功能的人源化骨结构。用经过 4 周培养的人间质祖细胞和 rhBMP-7 负载的可生物降解复合支架进行异位植入，可导致嵌合骨器官的发育，其中包含大量代谢活跃且能够建立支持人 HSCs 归巢和维持的人源化微环境的人间质细胞。使用同基因小鼠-小鼠移植实验证明了组织工程化听小骨的功能。我们预测，能够组织工程化具有形态完整和功能的大容量人源化骨髓腔的骨器官，将有助于进一步阐明人类 HSCs 与其天然龛位之间的生理或病理相互作用。
