3 years ago

Bone-healing capacity of conditioned medium derived from three-dimensionally-cultivated human mesenchymal stem cells and electrical stimulation on collagen sponge

Soon Jung Hwang, In Sook Kim, Tae Hyung Cho, Beaomseok Lee
Continuing from our previous study, we hypothesized that combining electrical stimulation (ES) and three-dimensional (3D) culture would be a useful strategy to obtain more bioactive factors in conditioned medium (CM) derived from human mesenchymal stem cells (hMSC). Our aim in this study was to investigate the bone-healing capacity of CM derived from hMSC after 4 days of culture on a collagen sponge-exposed (CM-ES) or unexposed (CM-control; CM-CON) to ES in comparison with that of hMSC implantation. A cytokine assay of both CMs revealed the presence of cytokines, growth factors and trophic factors. In vitro evaluation of both CMs showed increased cell growth and alkaline phosphatase activity of the hMSC, with little difference between CMs. We investigated the bone-healing effect using two bone disease models: bone defect and inflammatory bone loss. The calvaria defect was implanted with whole CM or 3D-precultured hMSC unexposed to ES. Microcomputed tomography analysis after 4 weeks indicated a two-fold greater bone volume in the CM-CON and CM-ES groups than in the hMSC and vehicle groups, though we found no difference between the CM groups. However, CM-ES enhanced the bone healing of IL-1-induced bone loss to a level comparable with hMSC, whereas CM-CON did not. These results show that 3D-cultured CM had a greater or similar capacity for bone healing as treatment using hMSC transplantation, and CM-ES was especially effective against inflammatory bone loss. Thus, 3D-cultured CM with or without ES presents an encouraging alternative to MSC-based bone healing. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jbm.a.36224

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