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Exp Ther Med. 2017 Nov;14(5):4111-4117. doi: 10.3892/etm.2017.5030. Epub 2017 Aug 25.

Growth/differentiation factor-5 promotes in vitro/vivo periodontal specific differentiation of induced pluripotent stem cell-derived mesenchymal stem cells.

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Department of Periodontology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, P.R. China.
Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, P.R. China.
Stem Cell Research Center and Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, P.R. China.


Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) represent a promising alternative source of MSCs for effective periodontal regeneration. Scientific evidence has demonstrated that growth/differentiation factor-5 (GDF-5) supports regeneration of periodontal tissues and has a key role in MSC differentiation. The present study investigated the effects of recombinant human GDF-5 (rhGDF-5) on periodontal specific differentiation of iPSC-derived MSCs (iPSC-MSCs) and bone marrow mesenchymal stem cells (BMSCs). rhGDF-5 treatment in vitro significantly enhanced the expression levels of marker genes associated with osteogenesis (OCN), fibrogenesis (periostin) and cementogenesis (CAP) in the iPSC-MSCs compared with untreated controls (all P<0.05). Interestingly, the rhGDF-5-treated BMSCs failed to exhibit overexpression of periostin and CAP despite highly upregulated expression of OCN. In the presence of rhGDF-5, both the iPSC-MSCs and BMSCs demonstrated marked formation of mineralized nodules. Notably, rhGDF-5 greatly promoted periodontal specific differentiation of the iPSC-MSCs encapsulated in hyaluronic acid (HA) hydrogels in vivo as determined by immunohistochemical and immunofluorescence staining. The majority of the PKH67-labeled iPSC-MSCs implanted with rhGDF-5 exhibited strong expression of OCN, periostin and CAP. In conclusion, iPSC-MSCs demonstrate high periodontal specific differentiation potential in response to rhGDF-5 both in vitro and in vivo. The delivery of iPSC-MSCs and rhGDF-5 with HA hydrogel may have beneficial effects in regenerative periodontal therapy.


differentiation; growth/differentiation factor-5; hydrogel; induced pluripotent stem cells; mesenchymal stem cells; periodontal regeneration

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