RESUMEN
Background and Objective: Oral and maxillofacial (OMF) defects caused by congenital conditions, injuries, ablative surgery for benign and malignant head & neck tumor, can often lead to OMF deformities and malfunctions in speech, mastication/chewing, and swallowing as well as have deleterious psychological effects and socioeconomic burdens to patients. Due to the unique complex 3D geometry of the head and neck region, reconstruction and rehabilitation of OMF defects remain a major challenge for OMF surgeons.The purpose of this narrative review is to update the information on the biological properties and functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their potential application in tissue engineering (TE) and regenerative reconstruction of OMF tissues. Methods: A data-based search was performed by using PubMed database whereby articles published between 2000 and 2021 in English were included in the search with the following key words: dental stem cells, OMF reconstruction, OMF TE and regeneration. Key Content and Findings: Currently, the advancement in stem cell biology, biomaterial science, and TE technology has demonstrated the significant potential application of stem cell-based therapy in regenerative reconstruction and rehabilitation of OMF defects. However, no stem cell-based product or device has been translated into clinical application to replace microsurgical free tissue transfer, the current mainstay of care in the reconstruction of OMF defects. Conclusions: Currently, microsurgical free tissue transfer remains the gold standard mainstay of care for the reconstruction of OMF defects due to their abundant blood supply and flexibility for transplantation. However, several major challenges, such as the limited availability, the requirement of a second surgery, donor site morbidity, and the risk of free flap failure, have promoted the development of novel approaches. Due to the advancement in stem cell biology, biomaterial science, and TE technology, stem cell-based regenerative therapy is emerging as a promising therapeutic approach for a variety of diseases, including regenerative reconstruction and rehabilitation of OMF defects. In this narrative review, we update on the characteristics and biological functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their released cell-free products, extracellular vesicles (EVs). We also highlighted their potential application in TE and regenerative reconstruction of OMF defects in animal models and clinical studies and the potential challenges in this field.
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BACKGROUND: Peripheral nerve injuries (PNIs) remain one of the great clinical challenges because of their considerable long-term disability potential. Postnatal neural crest-derived multipotent stem cells, including gingiva-derived mesenchymal stem cells (GMSCs), represent a promising source of seed cells for tissue engineering and regenerative therapy of various disorders, including PNIs. Here, we generated GMSC-repopulated nerve protectors and evaluated their therapeutic effects in a crush injury model of rat sciatic nerves. METHODS: GMSCs were mixed in methacrylated collagen and cultured for 48 h, allowing the conversion of GMSCs into Schwann-like cells (GiSCs). The phenotype of GiSCs was verified by fluorescence studies on the expression of Schwann cell markers. GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were co-cultured with THP-1-derived macrophages, and the secretion of anti-inflammatory cytokine IL-10 or inflammatory cytokines TNF-α and IL-1ß in the supernatant was determined by ELISA. In addition, GMSCs mixed in the methacrylated collagen were filled into a nerve protector made from the decellularized small intestine submucosal extracellular matrix (SIS-ECM) and cultured for 24 h, allowing the generation of functionalized nerve protectors repopulated with GiSCs. We implanted the nerve protector to wrap the injury site of rat sciatic nerves and performed functional and histological assessments 4 weeks post-surgery. RESULTS: GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were directly converted into Schwann-like cells (GiSCs) characterized by the expression of S-100ß, p75NTR, BDNF, and GDNF. In vitro, co-culture of GMSCs encapsulated in the 3D-collagen hydrogel with macrophages remarkably increased the secretion of IL-10, an anti-inflammatory cytokine characteristic of pro-regenerative (M2) macrophages, but robustly reduced LPS-stimulated secretion of TNF-1α and IL-1ß, two cytokines characteristic of pro-inflammatory (M1) macrophages. In addition, our results indicate that implantation of functionalized nerve protectors repopulated with GiSCs significantly accelerated functional recovery and axonal regeneration of crush-injured rat sciatic nerves accompanied by increased infiltration of pro-regenerative (M2) macrophages while a decreased infiltration of pro-inflammatory (M1) macrophages. CONCLUSIONS: Collectively, these findings suggest that Schwann-like cells converted from GMSCs represent a promising source of supportive cells for regenerative therapy of PNI through their dual functions, neurotrophic effects, and immunomodulation of pro-inflammatory (M1)/pro-regenerative (M2) macrophages.
