Zhao Andong, Chung Manhon, Yang Yi, Pan Xiaohua, Pan Yu, Cai Sa
Department of Trauma and Orthopedics, The 2nd Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen, China.
Plastic and Maxillofacial Surgery Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Curr Stem Cell Res Ther. 2023;18(2):216-230. doi: 10.2174/1574888X17666220510163245.
It has been observed that bone marrow-derived mesenchymal stem cells (MSCs) migrate towards the injured spinal cord and promote functional recovery when systemically transplanted into the traumatized spinal cord. However, the mechanisms underlying their migration to the spinal cord remain poorly understood.
In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into rat models of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis in regulating the migration of transplanted MSCs to the spinal cord. After intravenous injection, MSCs migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI rats promoted a dose-dependent migration of MSCs in culture, which was blocked by an inhibitor of CXCR4 or SDF-1 antibody.
The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to injured spinal cord tissues and may enhance neural regeneration. Modulation of the homing capacity may be instrumental in harnessing the therapeutic potential of MSCs.
据观察，骨髓间充质干细胞（MSCs）在全身移植到创伤性脊髓后会向损伤的脊髓迁移并促进功能恢复。然而，其迁移至脊髓的潜在机制仍知之甚少。
在本研究中，我们将表达绿色荧光蛋白（GFP）和荧光素酶的间充质干细胞全身移植到大鼠脊髓损伤模型中，并研究基质细胞衍生因子1（SDF-1）/CXCR4轴在调节移植的间充质干细胞向脊髓迁移中的作用。静脉注射后，间充质干细胞迁移至损伤的脊髓，此处SDF-1的表达增加。用CXCR4抑制剂预孵育可阻断间充质干细胞向脊髓的募集。它们的存在与形态和功能恢复相关。在体外，从脊髓损伤大鼠收集的SDF-1或脑脊液（CSF）可促进培养中间充质干细胞的剂量依赖性迁移，这被CXCR4抑制剂或SDF-1抗体阻断。
该研究表明，SDF-1/CXCR4相互作用将外源性间充质干细胞募集到损伤的脊髓组织，并可能增强神经再生。调节归巢能力可能有助于发挥间充质干细胞的治疗潜力。
