Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice

Abstract

BackgroundPeriodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model.MethodsIn the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation.ResultsOur study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm3) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm3) (P < 0.05). The percentage of bone in the periodontium in the hDPSC injection group was 12.8 ± 4.4 %, while it was 17.4 ± 5.3 % in the hDPSC sheet group (P < 0.05).ConclusionBoth hDPSC injection and cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0362-8) contains supplementary material, which is available to authorized users.

Stem cell‐based tooth and periodontal regeneration

“…Periodontal ligament cell sheets were used for periodontal regeneration in studies of dogs (Akizuki et al., ; Iwata et al., ). Besides PDLSCs (Ding, Liu, et al., ; Ding, Wang, et al., ; Liu et al., ), DPSCs (Hu et al., ; Khorsand et al., ), SHEDs (Fu, Jin, Ma, Fan, & Wang, ), BMMSCs (Du et al., ), ADSCs also have the potential for periodontal regeneration (Tobita & Mizuno, ).…”

Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration

“…Dental stem cell sheets have been shown to have advantages in odontogenic differentiation. [110][111][112] . However, which method is the most suitable for the neural differentiation of dental stem cells is still unclear.…”

“…A large amount of evidence has shown that stem cells, such as BMSCS and ADSCs, are available for tissue repair, including bone and muscle tissue, among others. Dental stem cell sheets have been shown to have advantages in odontogenic differentiation [110][111][112]. Dental stem cells possess greater promise over other sources of stem cells.…”

Spheroid formation and stemness preservation of human periodontal ligament cells on chitosan films

“…Current 3D cell culture systems consist of either 3D cell sheet constructs (Hu et al., ; Iwata et al., ; Panduwawala et al., ), 3D biomaterials encapsulated with cells (Aizawa & Shoichet, ; Kraehenbuehl, Langer, & Ferreira, ), or cellular spheroids (Baraniak & McDevitt, ; Cheng et al., ). 3D multilayered cell sheets are stacked in layers.…”

“…Consequently, it is straightforward to hypothesize that PDL cells cultured in 3D superiorly maintain their stemness compared with a 2D culture system. Current 3D cell culture systems consist of either 3D cell sheet constructs (Hu et al, 2016;Iwata et al, 2015;Panduwawala et al, 2017), 3D biomaterials encapsulated with cells (Aizawa & Shoichet, 2012;Kraehenbuehl, Langer, & Ferreira, 2011), or cellular spheroids (Baraniak & McDevitt, 2012;Cheng et al, 2012). 3D multilayered cell sheets are stacked in layers.…”