Potier E, Rivron N C, Van Blitterswijk C A, Ito K
Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
J Tissue Eng Regen Med. 2016 Dec;10(12):1021-1032. doi: 10.1002/term.1887. Epub 2014 Apr 2.
Although bone marrow stromal cells (BMSCs) appear promising for cartilage repair, current clinical results are suboptimal and the success of BMSC-based therapies relies on a number of methodological improvements, among which is better understanding and control of their differentiation pathways. We investigated here the role of the cellular environment (paracrine vs juxtacrine signalling) in the chondrogenic differentiation of BMSCs. Bovine BMSCs were encapsulated in alginate beads, as dispersed cells or as small micro-aggregates, to create different paracrine and juxtacrine signalling conditions. BMSCs were then cultured for 21 days with TGFβ added for 0, 7 or 21 days. Chondrogenic differentiation was assessed at the gene (type II and X collagens, aggrecan, TGFβ, sp7) and matrix (biochemical assays and histology) levels. The results showed that micro-aggregates had no beneficial effects over dispersed cells: matrix production was similar, whereas chondrogenic marker gene expression was lower for the micro-aggregates, under all TGFβ conditions tested. This weakened chondrogenic differentiation might be explained by a different cytoskeleton organization at day 0 in the micro-aggregates. Copyright © 2014 John Wiley & Sons, Ltd.
尽管骨髓基质细胞(BMSCs)在软骨修复方面前景广阔,但目前的临床效果并不理想,基于BMSCs的治疗方法的成功依赖于许多方法学上的改进,其中包括更好地理解和控制其分化途径。我们在此研究了细胞环境(旁分泌与近分泌信号传导)在BMSCs软骨分化中的作用。将牛BMSCs封装在藻酸盐珠中,作为分散细胞或小的微聚集体,以创建不同的旁分泌和近分泌信号传导条件。然后将BMSCs培养21天,添加TGFβ 0、7或21天。在基因(II型和X型胶原蛋白、聚集蛋白聚糖、TGFβ、sp7)和基质(生化分析和组织学)水平评估软骨分化。结果表明,在所有测试的TGFβ条件下,微聚集体对分散细胞没有有益作用:基质产生相似,但微聚集体的软骨生成标记基因表达较低。这种软骨分化减弱可能是由于微聚集体在第0天的细胞骨架组织不同所致。版权所有© 2014 John Wiley & Sons, Ltd.