In VivoExperiments with Dental Pulp Stem Cells for Pulp-Dentin Complex Regeneration

Abstract

In recent years, many studies have examined the pulp-dentin complex regeneration with DPSCs. While it is important to perform research on cells, scaffolds, and growth factors, it is also critical to develop animal models for preclinical trials. The development of a reproducible animal model of transplantation is essential for obtaining precise and accurate data in vivo. The efficacy of pulp regeneration should be assessed qualitatively and quantitatively using animal models. This review article sought to introduce in vivo experiments that have evaluated the potential of dental pulp stem cells for pulp-dentin complex regeneration. According to a review of various researches about DPSCs, the majority of studies have used subcutaneous mouse and dog teeth for animal models. There is no way to know which animal model will reproduce the clinical environment. If an animal model is developed which is easier to use and is useful in more situations than the currently popular models, it will be a substantial aid to studies examining pulp-dentin complex regeneration.

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

“…Previous studies have shown that dental MSCs, including DPSCs, SHED, and SCAP, have the capacity to differentiate into odontoblastic lineages in vitro and of regenerating dentin/pulp-like complexes or bone-like tissues ectopically and around teeth and implants [29, 31, 66] (the literature summarized in Table 2). …”

“…Recent studies have also proposed demineralized/chemically Treated Dentin Matrices (TDMs) [86] or Cryopreserved Treated Dentine Matrices (CTDM) [87], as ideal biologic scaffolds, because of their combination of favorable mechanical properties and ability to act as a reservoir of dentinogenesis-related growth/morphogenetic factors [88]; this is also validated by in vivo studies [89, 90]. Finally, strategies to improve stem cell/scaffold interfaces also include incorporation of various bioactive molecules [29], as the third component of the TE triad (cells/scaffolds/growth factors). The application of such growth factors without stem cells, in a cell homing versus cell transplantation strategy, has also been suggested as a more clinically translational approach for dentin-pulp regeneration.…”

“…It must be noted that a major problem concerning in vivo studies aiming at regenerating functional dentin-pulp complexes or bone around teeth and implants is the fact that the majority have been conducted in ectopic implantation models, mostly subcutaneously into immunocompromised mice [13, 29, 67, 76], and to a less extent in renal capsules of rats [113]. In contrast, only few attempts in orthotropic large-animal models (dogs or mini pigs) have been performed by a sole research group [70–73], probably in view of the considerable economic costs involved together with the ethical issues associated with animal welfare.…”

“…In vivo studies, mostly in ectopic but less often in orthotopic animal models, have supported their potential to reconstitute functional dentin/pulp complexes when mixed with ceramic substrates (such as, Hydroxyapatite Or Tricalcium Phosphate) [29, 30], as well as other tissues, such as bone [31], cementum [32], blood vessels [33–35], and neural tissues [36, 37]. Most recently, attention has been focused on the biological properties of the plethora of soluble trophic and immunomodulatory cytokines produced by dental MSCs (MSC secretome) because of their angiogenic, neurogenic, and tissue repair properties [38].…”

Stem Cells from Human Exfoliated Deciduous Teeth: Biology and Therapeutic Potential

“…It has been recently shown that SHEDs can generate functional dental pulp when injected with PuraMatrix or Collagen into root canals [19]. However, majority of the studies focusing on regenerating bone or dentin-pulp complex in vivo were performed in ectopic implantation models, mostly in skin or renal capsule, in mice or rats [20][21][22] which might not close to real clinical situation. More studies in the clinical relevance area such as tooth socket or jaw bone in larger animals such as pig or dog should be considered to make the results more valuable for application.…”