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用于疾病建模和药物测试的自组装人体骨骼类器官。

Self-assembling human skeletal organoids for disease modeling and drug testing.

机构信息

Department of Biomaterials, New York University College of Dentistry, New York, New York, USA.

Department of Biomedical Engineering, New York University Tandon School of Engineering, Brooklyn, New York, USA.

出版信息

J Biomed Mater Res B Appl Biomater. 2022 Apr;110(4):871-884. doi: 10.1002/jbm.b.34968. Epub 2021 Nov 27.

Abstract

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated "mini joint" cultures, which we used to model inflammatory disease and test Adenosine (A ) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

摘要

骨骼疾病是全球医疗体系面临的重大挑战。有效的治疗方法开发存在诸多障碍,包括缺乏准确的临床前组织和疾病模型。最近,人们尝试提出一种新的整体器官方法来模拟人类骨骼和软骨组织。这些自组装的骨骼类器官模拟了天然组织中存在的细胞环境和细胞外组织。骨类器官表现出成骨和微血管形成,软骨类器官显示出软骨发育和成熟的证据。源自骨骼和软骨组织的骨骼类器官自发地使它们的软骨和骨骼成分发生极化。我们使用这些混合骨骼类器官成功地生成了“微型关节”培养物,我们用其来模拟炎症性疾病,并测试腺嘌呤(A)受体激动剂作为治疗剂。这项工作及其结果表明,骨骼类器官可以作为一种有效的生物模型,用于组织发育和疾病研究,以及测试治疗剂。

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