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A potential therapy to enhance healing of bone tissue is to deliver isolated mesenchymal stem cells (MSCs) to the site of a lesion to promote bone formation. A key issue within this technology is the development of an injectable system for the delivery of MSCs. Fibrin gel exploits the final stage of the coagulation cascade in which fibrinogen molecules are cleaved by thrombin, convert into fibrin monomers and assembled into fibrils, eventually forming fibers in a three-dimensional network. This gel could have many advantages as a cell delivery vehicle in terms of biocompatibility, biodegradation and hemostasis. The objective of this study was to explore the possibility of using fibrin gel as a delivery system for human MSCs (HMSCs). To this end we have determined the optimal fibrinogen concentrations and thrombin activity for loading HMSCs in vitro into the resultant fibrin gels to obtain cell proliferation. We found that a concentration of 18 mg/ml of fibrinogen and a thrombin activity of 100 IU/ml was optimal for producing fibrin scaffolds that would allow good HMSCs spreading and proliferation. In these conditions, cells were able to proliferate and expressed alkaline phosphatase, a bone marker, in vitro. When implanted in vivo, HMSCs were able to migrate out of the fibrin gel and invade a calcium carbonate based ceramic scaffold suggesting that fibrin gel could serve as a delivery system for HMSCs.

Original publication

DOI

10.1016/s0142-9612(02)00618-x

Type

Journal article

Journal

Biomaterials

Publication Date

06/2003

Volume

24

Pages

2497 - 2502

Addresses

Laboratoire de Recherches Orthopédiques, UMR-CNRS 7052, Faculté de Médecine Lariboisière Saint-Louis, Université D. Diderot, 10 avenue de Verdun, Paris 75010, France.

Keywords

Cells, Cultured, Extracellular Matrix, Mesenchymal Stem Cells, Animals, Humans, Mice, Thrombin, Fibrin, Mesenchymal Stem Cell Transplantation, Culture Techniques, Cell Culture Techniques, Cell Division, Cell Survival, Aged, Aged, 80 and over, Middle Aged