Early tissue patterning recreated by mouse embryonic fibroblasts in a three-dimensional environment.
Cellular self-organization studies have been mainly focused on models such as Volvox, the slime mold Dictyostelium discoideum, and animal (metazoan) embryos. Moreover, animal tissues undergoing regeneration also exhibit properties of embryonic systems such as the self-organization process that rebuilds tissue complexity and function. We speculated that the recreation in vitro of the biological, biophysical, and biomechanical conditions similar to those of a regenerative milieu could elicit the intrinsic capacity of differentiated cells to proceed to the development of a tissue-like structure. Here we show that, when primary mouse embryonic fibroblasts are cultured in a soft nanofiber scaffold, they establish a cellular network that causes an organized cell contraction,proliferation, and migration that ends in the formation of a symmetrically bilateral structure with a distinct central axis. A subset of mesodermal genes (brachyury, Sox9, Runx2) is upregulated during this morphogenetic process. The expression of brachyury was localized first at the central axis, extending then to both sides of the structure. The spontaneous formation of cartilage-like tissue mainly at the paraxial zone followed expression ofSox9 and Runx2. Because cellular self-organization is an intrinsic property of the tissues undergoing development,this model could lead to new ways to consider tissue engineering and regenerative medicine.
Quintana
Lluís
L
Center for Biomedical Engineering, Massachusetts Institute of Technology, Boston, Massachusetts 02139, USA.
Muiños
Teresa Fernández
TF
Genove
Elsa
E
Del Mar Olmos
María
M
Borrós
Salvador
S
Semino
Carlos E
CE
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004622:Embryo, Mammalian; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009024:Morphogenesis; D049329:Nanostructures; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013997:Time Factors; D054457:Tissue Scaffolds; D000098908:Brachyury Protein
D050659:Core Binding Factor Alpha 1 Subunit; D005326:Fetal Proteins; D055758:SOX9 Transcription Factor; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C493716:Runx2 protein, mouse; C527933:Sox9 protein, mouse