TY - JOUR
T1 - Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes
AU - Kashpur, Olga
AU - Smith, Avi
AU - Gerami-Naini, Behzad
AU - Maione, Anna G.
AU - Calabrese, Rossella
AU - Tellechea, Ana
AU - Theocharidis, Georgios
AU - Liang, Liang
AU - Pastar, Irena
AU - Tomic-Canic, Marjana
AU - Mooney, David
AU - Veves, Aristidis
AU - Garlick, Jonathan A.
N1 - Funding Information:
This project was supported by U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK98055-06 (to J.A.G.). The authors declare no conflicts of interest.
Funding Information:
This project was supported by U.S. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK98055-06 (to J.A.G.). The authors declare no conflicts of interest.*%blankline%*
Publisher Copyright:
© FASEB.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - 3D in vitro skin tissue
KW - Chronic wound healing
KW - Extracellular matrix
KW - Migration
KW - Reprogramming
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U2 - 10.1096/fj.201801059
DO - 10.1096/fj.201801059
M3 - Article
C2 - 30088952
AN - SCOPUS:85059245267
VL - 33
SP - 1262
EP - 1277
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 1
ER -