Sargenti Azzurra, Pasqua Simone, Leu Marco, Dionisi Laura, Filardo Giuseppe, Grigolo Brunella, Gazzola Daniele, Santi Spartaco, Cavallo Carola
CellDynamics iSRL, 40136 Bologna, Italy.
abc biopply ag, 4500 Solothurn, Switzerland.
Bioengineering (Basel). 2023 Oct 12;10(10):1182. doi: 10.3390/bioengineering10101182.
Articular cartilage lacks intrinsic regenerative capabilities, and the current treatments fail to regenerate damaged tissue and lead only to temporary pain relief. These limitations have prompted the development of tissue engineering approaches, including 3D culture systems. Thanks to their regenerative properties and capacity to recapitulate embryonic processes, spheroids obtained from mesenchymal stromal cells are increasingly studied as building blocks to obtain functional tissues. The aim of this study was to investigate the capacity of adipose stromal cells to assemble in spheroids and differentiate toward chondrogenic lineage from the perspective of cartilage repair. Spheroids were generated by two different methods (3D chips vs. Ultra-Low Attachment plates), differentiated towards chondrogenic lineage, and their properties were investigated using molecular biology analyses, biophysical measurement of mass density, weight, and size of spheroids, and confocal imaging. Overall, spheroids showed the ability to differentiate by expressing specific cartilaginous markers that correlate with their mass density, defining a critical point at which they start to mature. Considering the spheroid generation method, this pilot study suggested that spheroids obtained with chips are a promising tool for the generation of cartilage organoids that could be used for preclinical/clinical approaches, including personalized therapy.
关节软骨缺乏内在的再生能力，目前的治疗方法无法使受损组织再生，只能暂时缓解疼痛。这些局限性促使了组织工程方法的发展，包括三维培养系统。由于间充质基质细胞来源的球体具有再生特性和重现胚胎发育过程的能力，因此越来越多地被研究作为构建功能组织的基本单元。本研究的目的是从软骨修复的角度研究脂肪基质细胞组装成球体并向软骨谱系分化的能力。通过两种不同方法（三维芯片与超低吸附板）生成球体，使其向软骨谱系分化，并使用分子生物学分析、球体质量密度、重量和大小的生物物理测量以及共聚焦成像来研究其特性。总体而言，球体通过表达与其质量密度相关的特定软骨标记物显示出分化能力，确定了它们开始成熟的临界点。考虑到球体生成方法，这项初步研究表明，用芯片获得的球体是生成软骨类器官的有前途的工具，可用于临床前/临床方法，包括个性化治疗。
