Department of Periodontology & Oral Medicine, School of Stomatology, Fourth Military Medical University, Xi'an, PR China.
Biomaterials. 2013 Sep;34(29):7033-47. doi: 10.1016/j.biomaterials.2013.05.025. Epub 2013 Jun 13.
Gingival tissue-derived mesenchymal stem cells (MSCs) were recently identified and characterized as having multipotential differentiation and immunomodulatory properties in vitro and in vivo, and they represent new postnatal stem cell types for cytotherapy and regenerative medicine. However, the utility of gingival MSCs (GMSCs) as alternatives to periodontal ligament stem cells (PDLSCs), which have been demonstrated to be effective but with limited cell availability and reduced clinical feasibility, for periodontal regeneration in a previously diseased/inflamed environment remains obscure. In this study, patient-matched human GMSCs and PDLSCs were evaluated in terms of their colony-forming ability, proliferative capacity, cell surface epitopes, multi-lineage differentiation potentials, and related gene expression when incubated in different designed culture conditions, with or without the presence of inflammatory cytokines. An in vivo ectopic transplantation model using transplants from inflammatory cytokine-treated or untreated cells was applied to assess bone formation. We found that cells derived from both tissues expressed MSC markers, including CD146, CD105, CD90, CD29, and STRO-1. Both cells successfully differentiated under osteogenic, adipogenic, and chondrogenic microenvironments; PDLSCs displayed a more effective differentiation potential in all of the incubation conditions compared to GMSCs (P < 0.01). Although inflammatory cytokine-treated GMSCs and PDLSCs are inferior to normally cultured, patient and tissue-matched cells in terms of their osteogenic capacity and regenerative potential (P < 0.05), they retain the capacity for osteoblastic and adipose differentiation, as well as ectopic bone formation, similar to what has been demonstrated for other MSCs. Interestingly, GMSCs exhibited fewer inflammation-related changes in terms of osteogenic potential in vitro and bone formation in vivo compared to PDLSCs (P < 0.01). These results suggest that both gingiva and PDL tissues are putative cell sources for future cytotherapeutic applications. Whether GMSCs act as an adjunctive or alternative cell source for cytotherapy of inflammatory periodontal disease warrants further investigation.
牙龈组织来源的间充质干细胞（MSCs）最近被鉴定和表征为具有多能性分化和免疫调节特性，无论是在体外还是体内，它们都代表了用于细胞治疗和再生医学的新型产后干细胞类型。然而，牙龈间充质干细胞（GMSCs）作为牙周韧带间充质干细胞（PDLSCs）的替代品的用途仍然不清楚，PDLSCs 已被证明具有有效性，但细胞可用性有限，临床可行性降低，用于先前患病/炎症环境中的牙周再生。在这项研究中，评估了患者匹配的人 GMSCs 和 PDLSCs 的集落形成能力、增殖能力、细胞表面表型、多谱系分化潜能以及在不同设计的培养条件下孵育时的相关基因表达，这些培养条件包括有无炎症细胞因子的存在。应用来自经炎症细胞因子处理或未经处理的细胞的移植的体内异位移植模型来评估骨形成。我们发现，源自两种组织的细胞均表达 MSC 标志物，包括 CD146、CD105、CD90、CD29 和 STRO-1。在成骨、成脂和成软骨微环境下，两种细胞均成功分化；与 GMSCs 相比，PDLSCs 在所有孵育条件下均显示出更有效的分化潜力（P<0.01）。尽管与正常培养的、患者和组织匹配的细胞相比，经炎症细胞因子处理的 GMSCs 和 PDLSCs 在成骨能力和再生潜力方面较差（P<0.05），但它们保留了成骨细胞和脂肪细胞分化以及异位骨形成的能力，与其他 MSCs 所表现出的能力相似。有趣的是，与 PDLSCs 相比，GMSCs 在体外成骨潜力和体内骨形成方面表现出较少的与炎症相关的变化（P<0.01）。这些结果表明，牙龈和牙周组织都是未来细胞治疗应用的潜在细胞来源。GMSCs 是否作为炎症性牙周病细胞治疗的辅助或替代细胞来源，值得进一步研究。
