联合胎盘间充质干细胞与导向纳米颗粒有效治疗糖尿病肾病小鼠模型。

BACKGROUND: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of cell therapies in treating DN. METHODS: We developed FeO coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. RESULTS: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. CONCLUSION: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.

背景：糖尿病肾病（DN）是糖尿病的一种常见并发症，也是影响患者死亡率的主要原因。先前的研究表明，胎盘间充质干细胞（PL-MSCs）可减轻糖尿病肾病动物模型的肾功能障碍。然而，间充质干细胞（MSCs）归巢到受损部位的能力有限，限制了其治疗潜力。因此，提高 PL-MSCs 归巢到靶组织的精确性对于细胞疗法治疗糖尿病肾病的成功至关重要。

方法：我们开发了 FeO 涂层的聚多巴胺纳米颗粒（NP）内化的 MSC，并在链脲佐菌素和高脂肪饮食诱导的糖尿病肾病小鼠模型中，使用外部磁场评估其治疗效果。

结果：我们的研究证实，NP 有效地被内化到 PL-MSCs 中，而不会损害其固有干细胞特性。PL-MSCs 的磁靶向显著提高了它们在糖尿病肾病小鼠肾组织中的归巢，与单独移植 PL-MSCs 相比，改善了肾功能。此外，PL-MSCs 的抗炎和抗纤维化特性在肾功能和结构的恢复中发挥了作用。

结论：这些结果表明，使用 PL-MSCs 的磁靶向治疗是治疗糖尿病肾病的一种有前途的方法。