Interdisciplinary Centre for Bioinformatics, Medical Faculty, University of Leipzig, Leipzig, Germany.
Curr Med Chem. 2010;17(21):2274-91. doi: 10.2174/092986710791331095.
Degenerative joint diseases caused by rheumatism, joint dysplasia or traumata are particularly widespread in countries with high life expectation. Although there is no absolutely convincing cure available so far, hyaline cartilage and bone defects resulting from joint destruction can be treated today by appropriate transplantations. Recently, procedures were developed based on autologous chondrocytes from intact joint areas. The chondrocytes are expanded in cell culture and subsequently transplanted into the defect areas of the affected joints. However, these autologous chondrocytes are characterized by low expansion capacity and the synthesis of extracellular matrix of poor functionality and quality. An alternative approach is the use of adult mesenchymal stem cells (MSCs). These cells effectively expand in 2D culture and have the potential to differentiate into various cell types, including chondrocytes. Furthermore, they have the ability to synthesize extracellular matrix with properties mimicking closely the healthy hyaline joint cartilage. Beside a more general survey of the architecture of hyaline cartilage, its composition and the pathological processes of joint diseases, we will describe here which advances were achieved recently regarding the development of closed, aseptic bioreactors for the production of autologous grafts for cartilage regeneration based on MSCs. Additionally, a novel mathematical model will be presented that supports the understanding of the growth and differentiation of MSCs. It will be particularly emphasized that such models are helpful to explain the well-known fact that MSCs exhibit improved growth properties under reduced oxygen pressure and limited supply with nutrients. Finally, it will be comprehensively shown how different analytical methods can be used to characterize MSCs on different levels. Besides discussing methods for non-invasive monitoring and tracking of the cells and the determination of their elastic properties, mass spectrometric methods to evaluate the lipid compositions of cells will be highlighted.
由风湿病、关节畸形或创伤引起的退行性关节疾病在预期寿命较高的国家尤为普遍。尽管目前还没有完全令人信服的治疗方法，但今天可以通过适当的移植来治疗关节破坏引起的透明软骨和骨缺损。最近，基于完整关节区域的自体软骨细胞开发了一些程序。软骨细胞在细胞培养中扩增，然后移植到受影响关节的缺陷区域。然而，这些自体软骨细胞的特点是扩增能力低，细胞外基质的合成功能和质量差。另一种方法是使用成体间充质干细胞（MSCs）。这些细胞在 2D 培养中能有效地扩增，并具有分化为多种细胞类型的潜力，包括软骨细胞。此外，它们具有合成细胞外基质的能力，其特性与健康的透明关节软骨非常相似。除了更全面地了解透明软骨的结构、组成和关节疾病的病理过程外，我们还将在这里描述最近在开发基于 MSCs 的自体移植物用于软骨再生的封闭、无菌生物反应器方面取得的进展。此外，还将提出一个新的数学模型，以支持对 MSCs 生长和分化的理解。特别强调的是，这些模型有助于解释 MSCs 在低氧压和有限营养供应下表现出更好的生长特性这一众所周知的事实。最后，将全面展示如何在不同水平上使用不同的分析方法来表征 MSCs。除了讨论用于细胞的非侵入性监测和跟踪以及确定其弹性特性的方法外，还将重点介绍用于评估细胞脂质组成的质谱方法。
