Defining an optimal stromal derived factor-1 presentation for effective recruitment of mesenchymal stem cells in 3D

ABSTRACT In “situ” tissue engineering is a promising approach in regenerative medicine, envisaging to potentiate the physiological tissue repair processes by recruiting the host's own cellular progenitors at the lesion site by means of bioactive materials. Despite numerous works focused the att...

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Published in:	Biotechnology and bioengineering Vol. 111; no. 11; pp. 2303 - 2316
Main Authors:	Iannone, Maria, Ventre, Maurizio, Pagano, Gemma, Giannoni, Paolo, Quarto, Rodolfo, Netti, Paolo Antonio
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-11-2014 Wiley Subscription Services, Inc
Subjects:	3D collagen gel Cell Movement Cells, Cultured Chemokine CXCL12 - metabolism Chemokines Chemotaxis Collagen Gene Expression Profiling Human behavior Humans Instructive mesenchymal stem cells Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - physiology Molecules Optimization Polymerase chain reaction Real-Time Polymerase Chain Reaction Receptors Receptors, CXCR4 - biosynthesis Recruitment Stem cells stromal derived factor-1 Three dimensional Tissue engineering stromal derived factor-1 3D collagen gel mesenchymal stem cells chemotaxis
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Summary:	ABSTRACT In “situ” tissue engineering is a promising approach in regenerative medicine, envisaging to potentiate the physiological tissue repair processes by recruiting the host's own cellular progenitors at the lesion site by means of bioactive materials. Despite numerous works focused the attention in characterizing novel chemoattractant molecules, only few studied the optimal way to present signal in the microenvironment, in order to recruit cells more effectively. In this work, we have analyzed the effects of gradients of stromal derived factor‐1 (SDF‐1) on the migratory behavior of human mesenchymal stem cells (MSCs). We have characterized the expression of the chemokine‐associated receptor, CXCR4, using cytofluorimetric and real‐time PCR analyses. Gradients of SDF‐1 were created in 3D collagen gels in a chemotaxis chamber. Migration parameters were evaluated using different chemoattractant concentrations. Our results show that cell motion is strongly affected by the spatio‐temporal features of SDF‐1 gradients. In particular, we demonstrated that the presence of SDF‐1 not only influences cell motility but alters the cell state in terms of SDF‐1 receptor expression and productions, thus modifying the way cells perceive the signal itself. Our observations highlight the importance of a correct stimulation of MSCs by means of SDF‐1 in order to implement on effective cell recruitment. Our results could be useful for the creation of a “cell instructive material” that is capable to communicate with the cells and control and direct tissue regeneration. Biotechnol. Bioeng. 2014;111: 2303–2316. © 2014 Wiley Periodicals, Inc. The definition of an optimal scheme of spatio‐temporal presentation of SDF‐1 to control and direct MSC recruitment was presented in this study. The aim of the work was to assess the combination, in terms of gradient features and dose, of the SDF‐1 signal that effectively recruits MSCs in a three dimensional collagen gel. Results reported by the authors are useful in a tissue engineering context for the development of “cell instructive materials” that are able to recruit stem cells to the injured site.
Bibliography:	istex:A24F25F5F6B536A641EA537E49226722FD7705ED ark:/67375/WNG-LGZRFVJL-S ArticleID:BIT25283 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-3592 1097-0290
DOI:	10.1002/bit.25283