Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes

Olga Kashpur, Avi Smith, Behzad Gerami-Naini, Anna G. Maione, Rossella Calabrese, Ana Tellechea, Georgios Theocharidis, Liang Liang, Irena Pastar, Marjana Tomic-Canic, David Mooney, Aristidis Veves, Jonathan A. Garlick

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Diabetic foot ulcers (DFUs) are a major complication of diabetes, and there is a critical need to develop novel cell-and tissue-based therapies to treat these chronic wounds. Induced pluripotent stem cells (iPSCs) offer a replenishing source of allogeneic and autologous cell types that may be beneficial to improve DFU wound-healing outcomes. However, the biologic potential of iPSC-derived cells to treat DFUs has not, to our knowledge, been investigated. Toward that goal, we have performed detailed characterization of iPSC-derived fibroblasts from both diabetic and nondiabetic patients. Significantly, gene array and functional analyses reveal that iPSC-derived fibroblasts from both patients with and those without diabetes are more similar to each other than were the primary cells from which they were derived. iPSC-derived fibroblasts showed improved migratory properties in 2-dimensional culture. iPSC-derived fibroblasts from DFUs displayed a unique biochemical composition and morphology when grown as 3-dimensional (3D), self-assembled extracellular matrix tissues, which were distinct from tissues fabricated using the parental DFU fibroblasts from which they were reprogrammed. In vivo transplantation of 3D tissues with iPSC-derived fibroblasts showed they persisted in the wound and facilitated diabetic wound closure compared with primary DFU fibroblasts. Taken together, our findings support the potential application of these iPSCderived fibroblasts and 3D tissues to improve wound healing.

Original languageEnglish (US)
Pages (from-to)1262-1277
Number of pages16
JournalFASEB Journal
Volume33
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • 3D in vitro skin tissue
  • Chronic wound healing
  • Extracellular matrix
  • Migration
  • Reprogramming

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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