title: iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins.
abstract: Reprogramming of somatic cells to induced pluripotent stem cells (iPSC) provides an important cell source to derive patient-specific cells for potential therapeutic applications. However, it is not yet clear whether reprogramming through pluripotency allows the production of differentiated cells with improved functional properties that may be beneficial in regenerative therapies. To address this, we compared the production and assembly of extracellular matrix (ECM) by iPSC-derived fibroblasts to that of the parental, dermal fibroblasts (BJ), from which these iPSC were initially reprogrammed, and to fibroblasts differentiated from human embryonic stem cells (hESC). iPSC- and hESC-derived fibroblasts demonstrated stable expression of surface markers characteristic of stromal fibroblasts during prolonged culture and showed an elevated growth potential when compared to the parental BJ fibroblasts. We found that in the presence of L: -ascorbic acid-2-phosphate, iPSC- and hESC-derived fibroblasts increased their expression of collagen genes, secretion of soluble collagen, and extracellular deposition of type I collagen to a significantly greater degree than that seen in the parental BJ fibroblasts. Under culture conditions that enabled the self-assembly of a 3D stromal tissue, iPSC- and hESC-derived fibroblasts generated a well organized, ECM that was enriched in type III collagen. By characterizing the functional properties of iPSC-derived fibroblasts compared to their parental fibroblasts, we demonstrate that these cells represent a promising, alternative source of fibroblasts to advance future regenerative therapies.
authors.affiliation: Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shamis
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Hewitt
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bear
authors.forename: Addy
authors.initials: A
authors.lastname: Alt-Holland
authors.forename: Hiba
authors.initials: H
authors.lastname: Qari
authors.forename: Mariam
authors.initials: M
authors.lastname: Margvelashvilli
authors.forename: Elana B
authors.initials: EB
authors.lastname: Knight
authors.forename: Avi
authors.initials: A
authors.lastname: Smith
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Garlick
mesh_terms: D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; C011669:ascorbate-2-phosphate; D003094:Collagen; D001205:Ascorbic Acid