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肌肉骨骼类器官:一种用于建立肌肉骨骼疾病个性化模型和开发再生疗法的新兴工具。

Musculoskeletal organoids: An emerging toolkit for establishing personalized models of musculoskeletal disorders and developing regenerative therapies.

作者信息

Liu Yuwei, Zhou Zhilong, Lu Gang, Zhang Xin, Shi Dongquan, Tong Liping, Chen Di, Tuan Rocky S, Li Zhong Alan

机构信息

Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, PR China; Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, PR China.

Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.

出版信息

Acta Biomater. 2025 Jun 15;200:158-186. doi: 10.1016/j.actbio.2025.05.037. Epub 2025 May 15.


DOI:10.1016/j.actbio.2025.05.037
PMID:40381929
Abstract

Musculoskeletal (MSK) conditions are the primary cause of physical disability globally. These disorders are physically and mentally debilitating and severely impact the patients' quality of life. As the median age of the world's population increases, there has been an intensifying urgency of developing efficacious therapies for various orthopaedic conditions. Furthermore, the highly heterogeneous nature of MSK conditions calls for a personalized approach to studying disease mechanisms and developing regenerative treatments. Organoids have emerged as an advanced approach to generating functional tissue/organ mimics in vitro, which hold promise in MSK regeneration, disease modeling, and therapeutic development. Herein, we review the preparation, characterization, and application of various MSK organoids. We highlight the potential of patient-specific organoids in the development of personalized medicine and discuss the challenges and opportunities in the future development of MSK organoids. STATEMENT OF SIGNIFICANCE: Despite decades of research, translation of MSK research into clinical applications remains limited, partially attributed to our inadequate understanding of disease mechanisms. To advance therapeutic development, there are critical needs for MSK disease models with higher clinical relevance and predictive power. Additionally, engineered constructs that closely mimic the structural and functional features of native MSK tissues are highly desirable. MSK organoids have emerged as a promising approach to meet the above requirements. To unleash the full potential of MSK organoids necessitates a comprehensive understanding of their categories, construction, development, functions, applications, and challenges. This review aims to fulfill this crucial need, aiming to accelerate the clinical translation of MSK organoid platforms to benefit millions of patients afflicted with MSK conditions.

摘要

肌肉骨骼(MSK)疾病是全球身体残疾的主要原因。这些疾病会导致身体和精神衰弱,严重影响患者的生活质量。随着世界人口年龄中位数的增加,开发针对各种骨科疾病的有效疗法变得愈发紧迫。此外,MSK疾病的高度异质性要求采用个性化方法来研究疾病机制和开发再生治疗方法。类器官已成为一种在体外生成功能性组织/器官模拟物的先进方法,在MSK再生、疾病建模和治疗开发方面具有潜力。在此,我们综述了各种MSK类器官的制备、表征和应用。我们强调了患者特异性类器官在个性化医学发展中的潜力,并讨论了MSK类器官未来发展中的挑战和机遇。重要性声明:尽管经过数十年的研究,但MSK研究转化为临床应用仍然有限,部分原因是我们对疾病机制的理解不足。为了推进治疗开发,迫切需要具有更高临床相关性和预测能力的MSK疾病模型。此外,非常需要能够紧密模拟天然MSK组织结构和功能特征的工程构建体。MSK类器官已成为满足上述要求的一种有前途的方法。要充分发挥MSK类器官的潜力,需要全面了解它们的类别、构建、发育、功能、应用和挑战。本综述旨在满足这一关键需求,旨在加速MSK类器官平台的临床转化,以使数百万患有MSK疾病的患者受益。

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