eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2017   Volume No 33 – pages 121-129

Title: Cell aggregation enhances bone formation by human mesenchymal stromal cells

Authors: A Chatterjea, VLS LaPointe, A Barradas, H Garritsen, H Yuan, A Renard, CA van Blitterswijk, J de Boer

Address: Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, 6229 ER Maastricht, The Netherlands

E-mail: jan.deboer at

Key Words: Bone tissue engineering, bone regeneration, calcium phosphate, mesenchymal stem cell.

Publication date: February 15th 2017

Abstract: The amount of bone generated using current tissue engineering approaches is insufficient for many clinical applications. Previous in vitro studies suggest that culturing cells as 3D aggregates can enhance their osteogenic potential, but the effect on bone formation in vivo is unknown. Here, we use agarose wells to generate uniformly sized mesenchymal stromal cell (MSC) aggregates. When combined with calcium phosphate ceramic particles and a gel prepared from human platelet-rich plasma, we generated a tissue engineered construct which significantly improved in vivo bone forming capacity as compared to the conventional system of using single cells seeded directly on the ceramic surface. Histology demonstrated the reproducibility of this system, which was tested using cells from four different donors. In vitro studies established that MSC aggregation results in an up-regulation of osteogenic transcripts. And finally, the in vivo performance of the constructs was significantly diminished when unaggregated cells were used, indicating that cell aggregation is a potent trigger of in vivo bone formation by MSCs. Cell aggregation could thus be used to improve bone tissue engineering strategies.

Article download: Pages 121-129 (PDF file)