Journal
STEM CELLS TRANSLATIONAL MEDICINE
Volume 9, Issue 3, Pages 403-415Publisher
OXFORD UNIV PRESS
DOI: 10.1002/sctm.19-0281
Keywords
human fibroblast; IGFBP7; IL-6; osteoblast; reprogramming; senescence
Categories
Funding
- National Health and Medical Research Council of Australia [APP1139515, APP1110219]
- Australian Research Council
- University of Sydney Bridging Fellowship
- National Health and Medical Research Council (NHMRC) Early Career Fellowships [APP1036370]
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The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans-differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans-differentiation of human fibroblasts into functional osteoblasts using insulin-like growth factor binding protein-7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared to those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL-6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans-differentiate fibroblasts to osteoblasts.
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