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

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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.

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Acknowledgments

We would like to thank Drs. Nimet Maherali and Konrad Hochedlinger for the BJ-iPSC line and Judith Edwards for help in preparation of this manuscript. This work was supported by grant no. DE017413 to JAG from National Institute for Dental Research (NIDCR).

Conflicts of interest

The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA

    Yulia Shamis, Kyle J. Hewitt & Jonathan A. Garlick

  2. Department of Biology, Pine Manor College, 400 Heath Street, Chestnut Hill, MA, 02167, USA

    Susan E. Bear

  3. Division of Cancer Biology and Tissue Engineering, Department of Endodontics, School of Dental Medicine, Tufts University, 136 Harrison Avenue, South Cove Bldg, Room 116, Boston, MA, 02111, USA

    Addy Alt-Holland

  4. Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, School of Dental Medicine, Tufts University, 136 Harrison Avenue, South Cove Bldg, Room 116, Boston, MA, 02111, USA

    Hiba Qari, Mariam Margvelashvilli, Elana B. Knight, Avi Smith & Jonathan A. Garlick

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  1. Yulia Shamis
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  2. Kyle J. Hewitt
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  9. Jonathan A. Garlick
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Correspondence to Jonathan A. Garlick.

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Editor: T. Okamoto

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Shamis, Y., Hewitt, K.J., Bear, S.E. et al. iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins. In Vitro Cell.Dev.Biol.-Animal 48, 112–122 (2012). https://doi.org/10.1007/s11626-011-9478-4

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  • DOI: https://doi.org/10.1007/s11626-011-9478-4

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