Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Dent Res. 2021 Jun;100(6):568-575. doi: 10.1177/0022034520985820. Epub 2021 Jan 21.
Successful tissue engineering therapies rely on the appropriate selection of the cell source, biomaterial, and regulatory factors. To be applied in a wide range of clinical applications, the ideal cell source needs to be easily accessible and abundant. Human orofacial tissues and teeth harbor several populations of mesenchymal stem cells (MSCs) with self-renewal and multilineage differentiation capabilities. The ease of access, relative abundance, and minimally invasive isolation procedures needed to harvest most types of the dental-derived MSCs render them a promising cell source for tissue engineering applications. A growing body of evidence has reported the profound immunoregulatory potential of dental-derived MSCs as compared with their bone marrow counterparts. Biomaterials can act as a physical barrier protecting the MSCs from the invasion of the immune system by hindering penetration of proinflammatory cells/cytokines, leading to higher viability of the encapsulated MSCs and improved tissue regeneration. Besides their protective capabilities, biomaterials can actively contribute to the immunoregulatory potential of the MSCs through their physical and chemical properties, including porosity and elasticity. However, despite recent advancement, the therapeutic capability of biomaterials to regulate the MSC-host immune system crosstalk and the mechanism underlying this immunoregulation has been poorly understood. It has been reported that biomaterials can regulate the viability and determine the fate of the encapsulated MSCs through modulation of the NF-kB pathway and the caspase-3 and caspase-8 proapoptotic cascades. Additionally, the physiomechanical properties of the encapsulating biomaterial have been shown to modulate clustering of TNF-α receptors on the encapsulated MSCs while regulating the production of anti-inflammatory factors such as indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE) through activation of the P38 MAPK pathway. In the current review, we sought to provide a thorough overview of the immunomodulatory functions of dental-derived MSCs and the role of biomaterials in their interplay with the host immune system.
成功的组织工程治疗依赖于细胞来源、生物材料和调节因子的适当选择。为了在广泛的临床应用中应用，理想的细胞来源需要易于获得且丰富。人类口腔颌面组织和牙齿中存在几种具有自我更新和多谱系分化能力的间充质干细胞（MSCs）。大多数类型的牙源性 MSCs 易于获取、相对丰富，且需要微创分离程序即可采集，这使它们成为组织工程应用的有前途的细胞来源。越来越多的证据表明，与骨髓来源的 MSC 相比，牙源性 MSC 具有更强的免疫调节潜力。生物材料可以作为物理屏障，通过阻止促炎细胞/细胞因子的渗透，保护 MSC 免受免疫系统的侵袭，从而提高包封 MSC 的存活率并改善组织再生。除了其保护能力外，生物材料还可以通过其物理和化学特性（包括孔隙率和弹性）积极贡献于 MSC 的免疫调节潜力。然而，尽管最近取得了进展，但生物材料调节 MSC-宿主免疫系统相互作用的治疗能力及其免疫调节的机制仍知之甚少。据报道，生物材料可以通过调节 NF-κB 途径和 caspase-3 和 caspase-8 促凋亡级联来调节 MSC 的活力并决定其命运。此外，包封生物材料的生理机械性能已被证明可以调节包封 MSC 上 TNF-α 受体的聚集，同时通过激活 P38 MAPK 途径调节抗炎因子（如吲哚胺 2,3-双加氧酶（IDO）和前列腺素 E2（PGE））的产生。在本综述中，我们试图全面概述牙源性 MSC 的免疫调节功能以及生物材料在其与宿主免疫系统相互作用中的作用。
