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Growth/differentiation factor5 promotes in vitro/vivo periodontal specific differentiation of induced pluripotent stem cellderived mesenchymal stem cells

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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 factor5 (GDF5) supports regeneration of periodontal tissues and has a key role in MSC differentiation. The present study investigated the effects of recombinant human GDF5 (rhGDF5) on periodontal specific differentiation of iPSCderived MSCs (iPSCMSCs) and bone marrow mesenchymal stem cells (BMSCs). rhGDF5 treatment in vitro significantly enhanced the expression levels of marker genes associated with osteogenesis (OCN), fibrogenesis (periostin) and cementogenesis (CAP) in the iPSCMSCs compared with untreated controls (all P<0.05). Interestingly, the rhGDF5treated BMSCs failed to exhibit overexpression of periostin and CAP despite highly upregulated expression of OCN. In the presence of rhGDF5, both the iPSCMSCs and BMSCs demonstrated marked formation of mineralized nodules. Notably, rhGDF5 greatly promoted periodontal specific differentiation of the iPSCMSCs encapsulated in hyaluronic acid (HA) hydrogels in vivo as determined by immunohistochemical and immunofluorescence staining. The majority of the PKH67labeled iPSCMSCs implanted with rhGDF5 exhibited strong expression of OCN, periostin and CAP. In conclusion, iPSCMSCs demonstrate high periodontal specific differentiation potential in response to rhGDF5 both in vitro and in vivo. The delivery of iPSCMSCs and rhGDF5 with HA hydrogel may have beneficial effects in regenerative periodontal therapy.
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Document Type: Research Article

Affiliations: 1: 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 2: Stem Cell Research Center and Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, P.R. China

Publication date: January 1, 2017

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  • Experimental and Therapeutic Medicine aims to ensure the expedient publication, in both print and electronic format, of studies relating to biology, gene therapy, infectious disease, microbiology, molecular cardiology and molecular surgery. The journal welcomes studies pertaining to all aspects of molecular medicine, and studies relating to in vitro or in vivo experimental model systems relevant to the mechanisms of disease are also included.

    All materials submitted to this journal undergo the appropriate review via referees who are experts in this field. All materials submitted follow international guidelines with regard to approval of experiments on humans and animals.
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