Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel

Objective: Gingival tissue is composed of cell types that contribute to the body’s defense against many agents in oral environment, wound healing and tissue regeneration. Thanks to their easy and scarcely invasive withdrawal procedure, interdental papilla provide a good source of mesenchymal stromal cells (GinPa-MSCs). We isolated GinPa-MSCs and verified their ability to uptake/release the anticancer agent Paclitaxel (PTX). Methods: In vitro expanded GinPa-MSCs were characterized for CD markers by FACS, tested for differentiation ability and analyzed by TEM. Their ability to uptake/release PTX was assessed according to a standardized procedure. Results: The CD expression and chondro-adipo-osteo differentiation ability confirmed the mesenchymal feature of GinPa-MSCs. Surprisingly, 28% of GinPa-MSCs expressed CD14 marker and had an impressive pinocytotic activity. GinPa-MSCs were able to take up and release a sufficient amount of PTX to demonstrate effective in vitro activity against pancreatic carcinoma cells, suggesting that the drug was not inactivated. Conclusions: The procedure to obtain MSCs from interdental papilla is less invasive than that used for both bone marrow and adipose tissue, GinPa-MSCs are easy to expand and can be efficiently loaded with PTX. Taken together these qualities suggest that GinPa-MSCs may prove to be a good tool for cell-mediated drug delivery in cancer, particularly if related to stomatognathic system.研究目的：牙龈组织由多种细胞类群组成，这些细胞可协助机体抵御口腔环境中的多种致病因子，并参与伤口愈合与组织再生过程。牙龈乳头（interdental papilla）的取材方式简便且侵袭性极低，因此其来源的间充质基质细胞（GinPa-MSCs）是优质的间充质干细胞来源。本研究分离了牙龈乳头来源间充质基质细胞（GinPa-MSCs），并验证了其摄取与释放抗癌药物紫杉醇（Paclitaxel, PTX）的能力。 实验方法：通过流式细胞术（FACS）对体外扩增的GinPa-MSCs进行CD标志物鉴定，检测其多向分化潜能，并通过透射电子显微镜（TEM）开展分析；同时依照标准化流程评估其摄取与释放PTX的能力。 实验结果：CD标志物表达谱以及软骨、脂肪、成骨三系分化能力均证实了GinPa-MSCs的间充质干细胞特性。令人意外的是，28%的GinPa-MSCs表达CD14标志物，且具备极强的胞饮活性。GinPa-MSCs能够摄取并释放足量的PTX，在体外对胰腺癌细胞展现出有效的抗肿瘤活性，提示药物并未发生失活。 研究结论：从牙龈乳头获取间充质干细胞的操作，相较于骨髓来源与脂肪组织来源的间充质干细胞取材方式，侵袭性显著更低；GinPa-MSCs易于体外扩增，且可高效负载PTX。综上，这些特性表明GinPa-MSCs有望成为癌症细胞介导药物递送的优质工具，尤其适用于口颌系统相关癌症的治疗。