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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1002/sctm.19-0281
Journal or Publication Title: STEM CELLS Translational Medicine
Volume: 9
Number: 3
Page Range: pp. 403-415
Date: 2020
Divisions: ACRF Centenary Cancer Research Centre
Depositing User: General Admin
Identification Number: 10.1002/sctm.19-0281
ISSN: 2157-6564
Date Deposited: 04 Jan 2021 04:01
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.

Significance statement
Bone tissue engineering is a growing field, where cell therapies have considerable translational potential. Current cell‐based approaches are constrained by a limited capacity to harvest osteoblasts, mesenchymal stem cells, and a poor osteogenic potential of isolated patient fibroblasts. This study describes an innovative approach for promoting the trans‐differentiation of human fibroblasts into functional osteoblasts using a single naturally bioactive protein, insulin growth factor binding protein‐7 (IGFBP7). This approach will have significant advantages over other commonly used cell sources, including iPSCs and adult mesenchymal stem cells, and will potentially lead to a shift in the current paradigm of bone regenerative medicine.

Creators:
Creators
Email
Lu, ZuFu
UNSPECIFIED
Chiu, Joyce
UNSPECIFIED
Lee, Lucinda R.
UNSPECIFIED
Schindeler, Aaron
UNSPECIFIED
Jackson, Miriam
UNSPECIFIED
Ramaswamy, Yogambha
UNSPECIFIED
Dunstan, Colin R.
UNSPECIFIED
Hogg, Philip J.
UNSPECIFIED
Zreiqat, Hala
UNSPECIFIED
Last Modified: 04 Jan 2021 04:01
URI: https://eprints.centenary.org.au/id/eprint/730

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