National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan, 610065, China.
College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan, 610065, China.
J Mater Chem B. 2021 Dec 15;9(48):9989-10002. doi: 10.1039/d1tb02319e.
Co-culture of chondrocytes and mesenchymal stem cells (MSCs) represents an effective way to stimulate the chondrogenesis of MSCs and reduce hypertrophy, but the limited donor site supply and the requirement of two-stage operations are among the major barriers of using autologous chondrocytes in clinical settings. With recent evidence indicating that the chondrogenic effects of the above co-culture mainly lied on the paracrine secretion, and that cell membranes also played crucial roles during the chondrocyte-MSC interaction, we fabricated a multifunctional design of "artificial chondrocytes", which consist of chondrocyte secretome enriched PLGA microparticles with the encapsulation of chondrocytes' membrane fragments. The artificial chondrocytes had shown a similar diameter and surface electrical charge to natural chondrocytes, with the preserved key chondrocyte membrane surface proteins and sustainedly released chondrogenic cytokines from the chondrocyte secretome to extend their effects . Consequently, the co-culture studies of artificial chondrocytes and bone marrow MSCs had shown the beneficial effects from both chondrocyte secretome and membrane fragments, which also synergistically facilitated the cell proliferation, chondrogenic gene expression, cartilaginous matrix production, and reduced phenotypic hypertrophy and . Together, this study has successfully developed the proof-of-concept design of "artificial chondrocytes", which could potentially conquer many major barriers of using natural chondrocytes and provided a novel synthetic-cell approach to current therapeutical strategies towards the functional regeneration of articular cartilage.
软骨细胞和间充质干细胞（MSCs）的共培养代表了一种有效刺激 MSCs 软骨分化和减少肥大的方法，但自体软骨细胞在临床应用中的主要障碍包括供体部位有限和需要两阶段手术。最近的证据表明，上述共培养的软骨生成作用主要取决于旁分泌分泌，细胞膜在软骨细胞-MSC 相互作用中也起着至关重要的作用，我们设计了一种“人工软骨细胞”的多功能设计，它由富含软骨细胞分泌物的 PLGA 微球组成，其中包含软骨细胞的膜片段。人工软骨细胞具有与天然软骨细胞相似的直径和表面电荷，保留了关键的软骨细胞表面蛋白，并持续从软骨细胞分泌物中释放软骨生成细胞因子，从而延长其作用。因此，人工软骨细胞和骨髓间充质干细胞的共培养研究显示了软骨细胞分泌物和膜片段的双重益处，这也协同促进了细胞增殖、软骨生成基因表达、软骨基质产生，并减少了表型肥大。总的来说，这项研究成功地开发了“人工软骨细胞”的概念验证设计，它有可能克服使用天然软骨细胞的许多主要障碍，并为当前关节软骨功能再生的治疗策略提供了一种新的合成细胞方法。
