Key Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.
Cell Prolif. 2023 Feb;56(2):e13354. doi: 10.1111/cpr.13354. Epub 2022 Oct 20.
Spina bifida aperta (SBA) is one of the most common neural tube defects. Neural injury in SBA occurs in two stages involving failed neural tube closure and progressive degeneration through contact with the amniotic fluid. We previously suggested that intra-amniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for fetal rat SBA could achieve beneficial functional recovery through lesion-specific differentiation. The aim of this study is to examine whether the amniotic fluid microenvironment can be improved by intra-amniotic BMSC transplantation.
The intra-amniotic BMSC injection was performed using in vivo rat fetal SBA models. The various cytokine expressions in rat amniotic fluid were screened by protein microassays. Intervention experiments were used to study the function of differentially expressed cytokines.
A total of 32 cytokines showed significant upregulated expression in the BMSC-injected amniotic fluid. We focused on Activin A, NGF, BDNF, CNTF, and CXCR4. Intervention experiments showed that the upregulated Activin A, NGF, BDNF, and CNTF could inhibit apoptosis and promote synaptic development in fetal spinal cords. Inhibiting the activity of these factors weakened the anti-apoptotic and pro-differentiation effects of transplanted BMSCs. Inhibition of CXCR4 activity reduced the engraftment rate of BMSCs in SBA fetuses.
BMSC transplantation can improve the amniotic fluid environment, and this is beneficial for SBA repair.
开放性脊柱裂（SBA）是最常见的神经管缺陷之一。SBA 中的神经损伤分两个阶段发生，涉及神经管闭合失败和与羊水接触后的进行性退化。我们之前提出，骨髓间充质干细胞（BMSC）宫内治疗胎鼠 SBA 可以通过病变特异性分化实现有益的功能恢复。本研究旨在研究宫内 BMSC 移植是否可以改善羊水微环境。
采用体内胎鼠 SBA 模型进行宫内 BMSC 注射。通过蛋白质微阵列筛选大鼠羊水中各种细胞因子的表达。干预实验用于研究差异表达细胞因子的功能。
共 32 种细胞因子在 BMSC 注射的羊水中有明显的上调表达。我们重点研究了激活素 A、NGF、BDNF、CNTF 和 CXCR4。干预实验表明，上调的激活素 A、NGF、BDNF 和 CNTF 可抑制胎脊髓中的细胞凋亡并促进突触发育。抑制这些因子的活性会减弱移植 BMSC 的抗凋亡和促分化作用。抑制 CXCR4 活性会降低 SBA 胎儿中 BMSC 的植入率。
BMSC 移植可以改善羊水环境，这有利于 SBA 修复。
