Developmental studies and 3D in vitro model systems show that the production and engagement of extracellular matrix (ECM) often precede stem cell differentiation. Yet, unclear is how the ECM triggers signaling events in sequence to accommodate multistep process characteristic of differentiation. Here, we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long-term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted prisms created from ECM proteins and associated controls. We found that exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.
Bibliographical noteFunding Information:
The authors thank Jerry Daniels, University of Minnesota Genomics Center, for careful processing of RNA samples via RNAseq. The authors acknowledge Alison Berman and Thomas Houghland for the technical assistance. The authors also thank Peiman Hematti, University of Wisconsin-Madison, for providing mesenchymal stem cells. Funding for this work was provided by the NSF Graduate Research Fellowship to Quyen A. Tran. NSF BME Award, 1445650. NIH R01 HL137204. NIH R01 HL131017.
Copyright © 2018 Quyen A.