In Vitro Cellular & Developmental Biology - Animal

, Volume 48, Issue 2, pp 112–122

iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins

  • Yulia Shamis
  • Kyle J. Hewitt
  • Susan E. Bear
  • Addy Alt-Holland
  • Hiba Qari
  • Mariam Margvelashvilli
  • Elana B. Knight
  • Avi Smith
  • Jonathan A. Garlick
Article

DOI: 10.1007/s11626-011-9478-4

Cite this article as:
Shamis, Y., Hewitt, K.J., Bear, S.E. et al. In Vitro Cell.Dev.Biol.-Animal (2012) 48: 112. doi:10.1007/s11626-011-9478-4

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.

Keywords

Induced pluripotent stem cellsHuman embryonic stem cellsFibroblastsAscorbic acidExtracellular matrix

Copyright information

© The Society for In Vitro Biology 2012

Authors and Affiliations

  • Yulia Shamis
    • 1
  • Kyle J. Hewitt
    • 1
  • Susan E. Bear
    • 2
  • Addy Alt-Holland
    • 3
  • Hiba Qari
    • 4
  • Mariam Margvelashvilli
    • 4
  • Elana B. Knight
    • 4
  • Avi Smith
    • 4
  • Jonathan A. Garlick
    • 1
    • 4
  1. 1.Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical SciencesTufts University School of MedicineBostonUSA
  2. 2.Department of BiologyPine Manor CollegeChestnut HillUSA
  3. 3.Division of Cancer Biology and Tissue Engineering, Department of Endodontics, School of Dental MedicineTufts UniversityBostonUSA
  4. 4.Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, School of Dental MedicineTufts UniversityBostonUSA