Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China.
Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
J Mol Histol. 2020 Aug;51(4):455-466. doi: 10.1007/s10735-020-09896-3. Epub 2020 Jul 12.
Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.
无细胞治疗是再生医学中的一种有效策略，因为它避免了免疫调节和稳定性等有争议的问题。最近，外泌体被探索作为干细胞治疗的一种有利替代物，因为它们具有多种优势，例如能够被内吞和固有生物相容性。本研究旨在研究人脱落乳牙来源的干细胞衍生的外泌体 (SHED-Exo) 对骨髓基质细胞 (BMSCs) 成骨和骨修复的影响。分离、鉴定并应用 SHED-Exo 于牙周炎引起的骨缺失区域的小鼠模型中。我们发现，SHED-Exo 的注射可使骨缺失恢复到与原始干细胞相同的程度。SHED-Exo 不影响 BMSCs 的增殖，轻度抑制细胞凋亡。此外，与 SHED 条件培养基相比，SHED-Exo 特异性促进 BMSCs 成骨并抑制成脂分化。BMSCs 与 SHED-Exo 共培养后，成骨标志物基因的表达、碱性磷酸酶活性和茜素红 S 染色显著增加。此外，Western blot 分析表明，Runx2（成骨分化的关键转录因子）和 p-Smad5 在 SHED-Exo 刺激下上调。外泌体存在时，脂肪标志物 PPARγ 的表达和脂滴的数量减少。低剂量的外泌体抑制炎症细胞因子 IL-6 和 TNF-α 的表达。总之，SHED-Exo 直接促进 BMSCs 的成骨、分化和骨形成。因此，外泌体具有用于治疗牙周炎和其他骨疾病的潜力。
