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Stem cells from deciduous tooth repair mandibular defect in swine.

ABSTRACT: Stem cells from human exfoliated deciduous teeth have been identified as a new post-natal stem cell population with multipotential differentiation capabilities, including regeneration of mineralized tissues in vivo. To examine the efficacy of utilizing these stem cells in regenerating orofacial bone defects, we isolated stem cells from miniature pig deciduous teeth and engrafted the critical-size bone defects generated in swine mandible models. Our results indicated that stem cells from miniature pig deciduous teeth, an autologous and easily accessible stem cell source, were able to engraft and regenerate bone to repair critical-size mandibular defects at 6 months post-surgical reconstruction. This pre-clinical study in a large-animal model, specifically swine, allows for testing of a stem cells/scaffold construct in the restoration of orofacial skeletal defects and provides rapid translation of stem-cell-based therapy in orofacial reconstruction in human clinical trials.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC2829885 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Stem cells from deciduous tooth repair mandibular defect in swine.

Zheng Y Y Liu Y Y Zhang C M CM Zhang H Y HY Li W H WH Shi S S Le A D AD Wang S L SL

Journal of dental research 20090301 3

Stem cells from human exfoliated deciduous teeth have been identified as a new post-natal stem cell population with multipotential differentiation capabilities, including regeneration of mineralized tissues in vivo. To examine the efficacy of utilizing these stem cells in regenerating orofacial bone defects, we isolated stem cells from miniature pig deciduous teeth and engrafted the critical-size bone defects generated in swine mandible models. Our results indicated that stem cells from miniatur ...[more]

PMID: 19329459

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Project description:Leigh syndrome is a highly heterogeneous condition caused by pathological mutations in either nuclear or mitochondrial DNA regions encoding molecules involved in mitochondrial oxidative phosphorylation, in which many organs including the brain can be affected. Among these organs, a high incidence of poor bone health has been recognized in primary mitochondrial diseases including Leigh syndrome. However, the direct association between mitochondrial dysfunction and poor bone health has not been fully elucidated. Mitochondrial biosynthesis is a potential therapeutic target for this syndrome, as it can ameliorate the impairment of oxidative phosphorylation without altering these gene mutations. A recent study has shown the impaired osteogenesis in the dental pulp stem cells derived from the deciduous teeth of a child with Leigh syndrome, harboring the heteroplasmic mutation G13513A in the mitochondrial DNA region encoding the ND5 subunit of the respiratory chain complex I. The present study aimed to investigate whether mitochondrial biogenesis could be a therapeutic target for improving osteogenesis, using the same stem cells in a patient-specific cellular model. For this purpose, bezafibrate was used because it has been reported to induce mitochondrial biogenesis as well as to improve bone metabolism and osteoporosis. Bezafibrate clearly improved the differentiation of patient-derived stem cells into osteoblasts and the mineralization of differentiated osteoblasts. The mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1α, ATP production, and mitochondrial Ca2+ levels were all significantly increased by bezafibrate in the patient-derived cells. In addition, the increased amount and morphological shift from the fragmentary to network shape associated with DRP1 downregulation were also observed in the bezafibrate-treated patient-derived cells. These results suggest that mitochondrial biogenesis may be a potential therapeutic target for improving osteogenesis in patients with Leigh syndrome, and bezafibrate may be one of the candidate treatment agents.

Project description:Large-size mandible graft has huge needs in clinic caused by infection, tumor, congenital deformity, bone trauma and so on. However, the reconstruction of large-size mandible defect is challenged due to its complex anatomical structure and large-range bone injury. The design and fabrication of porous implants with large segments and specific shapes matching the native mandible remain a considerable challenge. Herein, the 6% Mg-doped calcium silicate (CSi-Mg6) and β- and α-tricalcium phosphate (β-TCP, α-TCP) bioceramics were fabricated by digital light processing as the porous scaffolds of over 50% in porosity, while the titanium mesh was fabricated by selective laser melting. The mechanical tests showed that the initial flexible/compressive resistance of CSi-Mg6 scaffolds was markedly higher than that of β-TCP and α-TCP scaffolds. Cell experiments showed that these materials all had good biocompatibility, while CSi-Mg6 significantly promoted cell proliferation. In the rabbit critically sized mandible bone defects (∼13 mm in length) filled with porous bioceramic scaffolds, the titanium meshes and titanium nails were acted as fixation and load bearing. The results showed that the defects were kept during the observation period in the blank (control) group; in contrast, the osteogenic capability was significantly enhanced in the CSi-Mg6 and α-TCP groups in comparison with the β-TCP group, and these two groups not only had significantly increased new bone formation but also had thicker trabecular and smaller trabecular spacing. Besides, the CSi-Mg6 and α-TCP groups showed appreciable material biodegradation in the later stage (from 8 to 12 weeks) in comparison with the β-TCP scaffolds while the CSi-Mg6 group showed much outstanding mechanical capacity in vivo in the early stage compared to the β-TCP and α-TCP groups. Totally, these findings suggest that the combination of customized strength-strong bioactive CSi-Mg6 scaffolds together with titanium meshes is a promising way for repairing the large-size load-bearing mandible defects.

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Stem cells from deciduous tooth repair mandibular defect in swine.

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Stem cells from deciduous tooth repair mandibular defect in swine.

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