Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth

Abstract

Transplantation of bone marrow mesenchymal stem cells (BMDCs) into a denervated side of the spinal cord was reported to be a useful option for axonal regeneration. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. Cultured reassociations between dissociated embryonic dental mesenchymal and epithelial cells and implantation lead to a vascularized tooth organ regeneration. However, when reassociations were coimplanted with a trigeminal ganglion (TG), innervation did not occur. On the other hand, reassociations between mixed embryonic dental mesenchymal cells and bone marrow-derived cells isolated from green fluorescent protein (GFP) transgenic mice (BMDCs-GFP) (50/50) with an intact and competent dental epithelium (ED14) were innervated. In the present study, we verified the stemness of isolated BMDCs, confirmed their potential role in the innervation of bioengineered teeth, and analyzed the mechanisms by which this innervation can occur. For that purpose, reassociations between mixed embryonic dental mesenchymal cells and BMDCs-GFP with an intact and competent dental epithelium were cultured and coimplanted subcutaneously with a TG for 2 wk in ICR mice. Axons entered the dental pulp and reached the odontoblast layer. BMDCs-GFP were detected at the base of the tooth, with some being present in the pulp associated with the axons. Thus, while having a very limited contribution in tooth formation, they promoted the innervation of the bioengineered teeth. Using quantitative reverse transcription polymerase chain reaction and immunostainings, BMDCs were shown to promote innervation by 2 mechanisms: 1) via immunomodulation by reducing the number of T lymphocytes (CD3+, CD25+) in the implants and 2) by expressing neurotrophic factors such as NGF, BDNF, and NT3 for axonal growth. This strategy using autologous mesenchymal cells coming from bone marrow could be used to innervate bioengineered teeth without treatment with an immunosuppressor such as cyclosporine A (CsA), thus avoiding multiple side effects.

Bioengineered Tooth-A New Horizon

“…Dental tissue engineering is a new promising therapeutic approach that aims to replace the missing tooth with a bioengineered tooth or to restore the damaged dental tissue. The ability to obtain and manipulate postnatal tissues easily from individuals to generate biologic replacement tooth materials, such as dentin, enamel, and periodontal ligament, or, even better, replace teeth of predetermined size and shape entirely, is extremely valuable [4]. Mesenchymal stem cells can be obtained with ease from dental/ oral tissue, making them an attractive source of autologous stem cells.…”

Tooth Formation: Are the Hardest Tissues of Human Body Hard to Regenerate?

“…Recently, Strub et al recombined embryonic dental epithelium with a mixture of dental mesenchymal cells and bone marrow-derived cells and cultured and implanted these cells subcutaneously. The tooth-like tissues obtained were innervated with axons entering the newly formed pulp [214].…”

The Role of Medicine and Technology in Shaping the Future of Oral Health

“…20 Other researchers developed a strategy that allows autologous mesenchymal cells derived from bone marrow to supply nerves to bioengineered teeth. 21 These exciting developments point toward a future where damaged teeth could be restored completely and biologically without the use of crowns and fillings.…”