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再生医学中的间充质干细胞:聚焦于关节软骨和椎间盘再生。

Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.

作者信息

Richardson Stephen M, Kalamegam Gauthaman, Pushparaj Peter N, Matta Csaba, Memic Adnan, Khademhosseini Ali, Mobasheri Reza, Poletti Fabian L, Hoyland Judith A, Mobasheri Ali

机构信息

Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom.

Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia.

出版信息

Methods. 2016 Apr 15;99:69-80. doi: 10.1016/j.ymeth.2015.09.015. Epub 2015 Sep 15.

Abstract

Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

摘要

肌肉骨骼疾病是全球残疾和发病的主要原因,给卫生和社会护理系统带来巨大成本。基于细胞的疗法在包括肌肉骨骼疾病在内的多个疾病领域迅速发展。能够有效治疗关节和脊柱退变的新型生物疗法是再生医学的重中之重。从骨髓(BM-MSCs)、脂肪组织(AD-MSCs)和脐带(UC-MSCs)中分离出的间充质干细胞(MSCs)在软骨和椎间盘(IVD)修复方面显示出巨大的应用前景。这篇综述文章聚焦于在全球肌肉骨骼疾病负担不断增加的背景下,基于干细胞的软骨和IVD修复疗法。我们讨论了MSCs和软骨祖细胞的生物学特性,特别关注脐带/华通氏胶来源的MSCs,并研究它们在再生应用中的潜力。我们还总结了负责软骨形成控制的分子机制和信号通路的关键组成部分,并探索用于关节软骨和IVD再生的仿生支架和生物材料。这篇综述探讨了MSCs带来的令人兴奋的机遇,并讨论了与软骨和IVD修复及再生相关的挑战。在分离、扩增、分化和预处理MSCs以便随后植入退变的关节和脊柱方面,仍然存在许多技术挑战。然而,将生物材料与包含软骨细胞、软骨祖细胞和MSCs的基于细胞的疗法相结合的前景,使人们乐观地认为,跨学科方法将在不久的将来在再生肌肉骨骼组织(如关节和脊柱)方面取得重大突破。

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