Therapeutic potential of mesenchymal stem cells for oral and systemic diseases

Abstract

Mesenchymal stem cells (MSCs) are adult stem cells whose self-renewal, multipotency, and immunosuppressive functions have been investigated for therapeutic applications. MSCs have used for various systemic organ regenerative therapies, allowing rescue of tissue function in damaged or failing organs. This article reviews the regenerative and immunomodulatory functions of MSCs and their applications in dental, orofacial, and systemic tissue regeneration and treatment of inflammatory disorders. It also addresses challenges to MSC-mediated therapeutics arising from tissue and MSC aging and host immune response against allogenic MSC transplantation, and discusses alternative sources of MSCs aimed at overcoming these limitations.

Figure 1. Dental tissue regeneration using dMSCs

(A) Direct pulp capping is performed for immature tooth with open apices to preserve the pulp vitality and allow complete root formation. (B) Pulp revitalization aids in restoration of pulp vitality in necrotic teeth with immature root formation. This procedure also enhances root stability by continued formation of root structure. (C) Pulp tissue engineering restores pulp vitality in necrotic, mature teeth. This procedure would be an alternative to conventional RCT yet would preclude need to remove tooth structure for shaping purposes for root canal obturation. In doing so, excessive removal of root structure is not necessary, leading to longer and stable dentition. (D) PDL regeneration would allow management of avulsed teeth for delayed replantation. Other applications would be to regeneration PDL in extracted teeth for autotransplantation and around metal implants.

Figure 2. Dentin-pulp regeneration in young permanent tooth

(A) Carious lesion on tooth #30 of 9 y.o. patient was excavated and the defect repaired by direct pulp capping using mineral trioxide aggregate (MTA). (B) Immediately after treatment, pulp exposure was covered with MTA. (C) There is radiographically visible reparative dentin formation underneath MTA after six months postoperatively, demonstrating robust regenerative potential. (D) Tooth #3 from a 50 y.o. patient demonstrate heavily calcified pulp and root canal.

Figure 3. Immunomodulatory functions of MSCs

MSCs modulate both innate and adaptive immunity by inhibition proliferation of NK cells, B cells, and T cells. MSCs interfere with monocyte differentiation by inhibiting dendritic cell maturation. In contrast, MSCs induce Treg cells, maintaining tolerance to selfantigens.

Figure 4. Epithelial-mesenchymal transition induced by transduction of ΔNp63α

Rapidly proliferating normal human epidermal keratinocytes were retrovirally transduced with ΔNp63α. As control, empty vector (LXSN) was used as mock viral infection. Arrow indicates emerging mesenchymal cells that have lost the expression of E-Cadherin (E-Cad), which is shown as green staining. Blue nuclear staining was performed with DAPI. DIC, differential interference contrast.