title: Substrate stiffness and composition specifically direct differentiation of induced pluripotent stem cells.
abstract: Substrate stiffness, biochemical composition, and matrix topography deeply influence cell behavior, guiding motility, proliferation, and differentiation responses. The aim of this work was to determine the effect that the stiffness and protein composition of the underlying substrate has on the differentiation of induced pluripotent stem (iPS) cells and the potential synergy with specific soluble cues. With that purpose, murine iPS-derived embryoid bodies (iPS-EBs) were seeded on fibronectin- or collagen I-coated polyacrylamide (pAA) gels of tunable stiffness (0.6, 14, and 50 kPa) in the presence of basal medium; tissue culture polystyrene plates were employed as control. Specification of iPS cells toward the three germ layers was analyzed, detecting an increase of tissue-specific gene markers in the pAA matrices. Interestingly, soft matrix (0.6 kPa) coated with fibronectin favored differentiation toward cardiac and neural lineages and, in the case of neural differentiation, the effect was potentiated by the addition of specific soluble factors. The generation of mature astrocytes, neural cells, and cardiomyocytes was further proven by immunofluorescence and transmission electron microscopy. In summary, this work emphasizes the importance of using biomimetic matrices to accomplish a more specific and mature differentiation of stem cells for future therapeutic applications.
authors: 1 Laboratory of Cell Therapy, Division of Oncology, Foundation for Applied Medical Research, University of Navarra , Pamplona, Spain .
authors: Laura
authors: L
authors: Macrí-Pellizzeri
authors: Beatriz
authors: B
authors: Pelacho
authors: Ana
authors: A
authors: Sancho
authors: Olalla
authors: O
authors: Iglesias-García
authors: Ana María
authors: AM
authors: Simón-Yarza
authors: Mario
authors: M
authors: Soriano-Navarro
authors: Susana
authors: S
authors: González-Granero
authors: José Manuel
authors: JM
authors: García-Verdugo
authors: Elena M
authors: EM
authors: De-Juan-Pardo
authors: Felipe
authors: F
authors: Prosper
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001696:Biomechanical Phenomena / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D058732:Embryoid Bodies / Q000166:cytology / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000099166:Polyacrylamides