Department of Medical Ultrasound, Laboratory of Ultrasound Imaging Drug, West China Hospital of Sichuan University, Chengdu, China.
Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
J Cell Mol Med. 2020 Sep;24(18):10816-10829. doi: 10.1111/jcmm.15706. Epub 2020 Aug 17.
Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell-derived factor-1α (SDF-1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF-1α-loaded microbubbles MB(SDF-1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF-1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF-1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF-1α) through covalent bonding with impressive SDF-1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF-1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF-1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF-1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.
骨关节炎（OA）是中老年人常见的关节疾病，具有明显的软骨损伤，软骨再生是缓解或治疗 OA 的关键。在干细胞治疗中，骨髓间充质干细胞（BMSC）已被证实具有软骨再生能力。然而，干细胞在促进关节软骨再生中的作用受到其归巢率低的严重限制。基质细胞衍生因子-1α（SDF-1α）在 MSC 迁移中起重要作用，涉及激活、动员、归巢和保留。因此，我们旨在开发负载 SDF-1α的微泡 MB（SDF-1α），并通过体外和体内实验验证超声联合 MB（SDF-1α）对 BMSC 迁移的影响。在体外检查了微泡的特性和 SDF-1α 的含量。为了评估超声联合趋化性微泡对干细胞迁移的影响，将 BMSCs 局部和静脉注射到 OA 模型的膝关节中，并检测软骨中 BMSCs 的标志物。我们通过共价键成功制备了 MB（SDF-1α），具有令人印象深刻的 SDF-1α 载药效率和载药量。体外研究表明，超声联合 MB（SDF-1α）组可促进更多的干细胞迁移，具有最高的迁移细胞数、良好的细胞活力和最高的 CXCR4 表达。体内实验表明，在有或没有外源性 BMSC 给药的情况下，超声联合 MB（SDF-1α）组中出现了更多的 BMSC 表面标志物。因此，超声联合 MB（SDF-1α）可以促进 BMSC 向软骨归巢，为 OA 提供一种新的有前途的治疗方法。
