Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta.
Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta.
复制标题
羊膜腔内移植脑源性神经营养因子修饰间充质干细胞治疗先天性脊柱裂胎鼠
DOI：
10.1186/s13287-022-03105-6
复制
发表时间：
2022-08-13
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
开放性脊柱裂（SBA）是一种相对常见的神经管缺陷临床类型。虽然产前胎儿手术已被证明是一种有效的治疗SBA，神经功能的恢复仍然不令人满意，由于神经元缺陷。我们以前的研究结果表明，羊膜腔内移植的骨髓间充质干细胞（BMSCs）可以通过病变特异性植入和再生来保护神经功能。为进一步优化BMSCs的作用，改善脊髓缺损的环境，使其更有利于神经修复，本研究采用脑源性神经营养因子（brain-derived neurotrophic factor，BDNF-BMSCs）修饰羊膜内移植的BMSCs，验证BDNF-BMSCs的治疗潜力。体外用腺病毒介导的绿色荧光蛋白和脑源性神经营养因子（brain-derived neurotrophic factor，Ad-GFP-BDNF）修饰骨髓基质细胞，将其移植到全反式维甲酸（all-trans-retinoic acid，ATRA）诱导的15 d开放性脊柱裂大鼠胚胎羊膜腔内。采用免疫荧光、western blot和实时定量PCR技术检测不同神经元标志物和脊髓损伤相关基因的表达。在胚胎第20天测量开放性脊柱裂胎鼠的病变面积。采用90种细胞因子的蛋白质芯片检测BDNF-BMSCs羊膜内移植后微环境的变化。我们发现BDNF-BMSCs具有定向迁移的特性，移植于SBA损伤区，增加了缺损脊髓中BDNF的表达，减轻了脊髓细胞的凋亡，分化为神经元和皮肤样细胞，缩小了皮肤损伤面积，改善了羊水微环境。BDNF修饰的BMSCs在抑制细胞凋亡和促进神经分化方面优于单纯BMSCs。这些发现共同表明，羊膜内移植BDNF-BMSCs具有促进SBA胎儿缺陷神经组织恢复的优势。在线版本包含补充材料，可通过10.1186/s13287-022-03105-6获得。
Spina bifida aperta (SBA) is a relatively common clinical type of neural tube defect. Although prenatal fetal surgery has been proven to be an effective treatment for SBA, the recovery of neurological function remains unsatisfactory due to neuron deficiencies. Our previous results demonstrated that intra-amniotic transplanted bone marrow mesenchymal stem cells (BMSCs) could preserve neural function through lesion-specific engraftment and regeneration. To further optimize the role of BMSCs and improve the environment of defective spinal cords so as to make it more conducive to nerve repair, the intra-amniotic transplanted BMSCs were modified with brain-derived neurotrophic factor (BDNF-BMSCs), and the therapeutic potential of BDNF-BMSCs was verified in this study. BMSCs were modified by adenovirus encoding a green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) in vitro and then transplanted into the amniotic cavity of rat fetuses with spina bifida aperta which were induced by all-trans-retinoic acid on embryonic day 15. Immunofluorescence, western blot and real-time quantitative PCR were used to detect the expression of different neuron markers and apoptosis-related genes in the defective spinal cords. Lesion areas of the rat fetuses with spina bifida aperta were measured on embryonic day 20. The microenvironment changes after intra-amniotic BDNF-BMSCs transplantation were investigated by a protein array with 90 cytokines. We found that BDNF-BMSCs sustained the characteristic of directional migration, engrafted at the SBA lesion area, increased the expression of BDNF in the defective spinal cords, alleviated the apoptosis of spinal cord cells, differentiated into neurons and skin-like cells, reduced the area of skin lesions, and improved the amniotic fluid microenvironment. Moreover, the BDNF-modified BMSCs showed a better effect than pure BMSCs on the inhibition of apoptosis and promotion of neural differentiation. These findings collectively indicate that intra-amniotic transplanted BDNF-BMSCs have an advantage of promoting the recovery of defective neural tissue of SBA fetuses. The online version contains supplementary material available at 10.1186/s13287-022-03105-6.
登录
查看更多内容
肛门直肠畸形胎鼠支配肛提肌的感觉神经元发育缺陷
DOI：
10.1002/bdra.20576
发表时间：
2009-07-01
影响因子：
--
作者：
Guan, Kaoping;Li, Hui;Yuan, Zhengwei
通讯作者：
Yuan, Zhengwei
影响因子：
4.7
作者：
Lee, J;Duan, W;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
5.3
作者：
Danzer, E;Schwarz, U;Flake, AW
通讯作者：
Flake, AW
影响因子：
7.5
作者：
Fang Z;Chen P;Tang S;Chen A;Zhang C;Peng G;Li M;Chen X
通讯作者：
Chen X
影响因子：
4.3
作者：
Eyileten C;Kaplon-Cieslicka A;Mirowska-Guzel D;Malek L;Postula M
通讯作者：
Postula M