Reprogramming of human fibroblasts into osteoblasts by insulin-like growth factor-binding protein 7

Abstract

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 with 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.

Comparative transcriptome profiles of large and small bodied large-scale loaches cultivated in paddy fields

“…The binding protein of IGFs genes (IGFBPs) are known to inhibit cell growth and differentiation by binding specifically IGFs 38 , 39 , which can be influenced by many factors. Previous studies have shown that fasting increases hepatic IGFBPs levels, and IGFBPs drops back to normal after refeeding 11 , 40 .…”

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“…As fibroblasts display a great degree of in vitro morphological similarity to osteoblasts and possess similar transcriptional profiles (while lacking crucial osteoblast‐specific transcripts), 21,22 researchers led by Zufu Lu and Hala Zreiqat (University of Sydney, NSW, Australia) hypothesized that distinct factors produced by osteoblasts might induce transdifferentiation of fibroblasts into osteoblast‐like cells. As reported in their recent STEM CELLS Translational Medicine article, Lu et al established that the IGFBP7‐mediated transdifferentiation of fibroblasts to osteoblasts may represent a novel bone repair/regeneration strategy 11 . After discovering that media conditioned by human osteoblasts stimulated the reprogramming of human fibroblasts to functional osteoblasts, the authors undertook a proteomic analysis in the hope of identifying the factors crucial to this process.…”

“…In the second of our Featured Articles published this month in STEM CELLS , Kang et al report that the differentiation of transplanted hematopoietic stem cells (HSCs) into osteoblasts that lay down normal collagen can improve outcomes in a mouse model of brittle bone disease 10 . In a Related Article published recently in STEM CELLS Translational Medicine , Lu et al described how the expression of insulin growth factor binding protein‐7 (IGFBP7) in human fibroblasts induced their transdifferentiation into functional osteoblasts 11 …”

The role of menin in bone pathology

“…In particular, stem cells can form teratomas, their collection is a traumatic procedure, and they also lose their ability to differentiate after five passages. Dermal fibroblasts are capable to undergo 15 passages, but they are differentiated cells, and it is challenging to redirect them toward specific lineages ( 10 ).…”