Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta
Abstract Background 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 result...
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BMC
2022-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-03105-6 |
| _version_ | 1798042475241144320 |
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| author | Wei Ma Xiaowei Wei Hui Gu Dan Liu Wenting Luo Songying Cao Shanshan Jia Yiwen He Lizhu Chen Yuzuo Bai Zhengwei Yuan |
| author_facet | Wei Ma Xiaowei Wei Hui Gu Dan Liu Wenting Luo Songying Cao Shanshan Jia Yiwen He Lizhu Chen Yuzuo Bai Zhengwei Yuan |
| author_sort | Wei Ma |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusion These findings collectively indicate that intra-amniotic transplanted BDNF-BMSCs have an advantage of promoting the recovery of defective neural tissue of SBA fetuses. |
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| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-11T22:36:02Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-b07be390af05458583cf6aee264382572022-12-22T03:59:13ZengBMCStem Cell Research & Therapy1757-65122022-08-0113111410.1186/s13287-022-03105-6Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida apertaWei Ma0Xiaowei Wei1Hui Gu2Dan Liu3Wenting Luo4Songying Cao5Shanshan Jia6Yiwen He7Lizhu Chen8Yuzuo Bai9Zhengwei Yuan10Key Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityDepartment of Ultrasound, Shengjing Hospital, China Medical UniversityDepartment of Pediatric Surgery, Shengjing Hospital, China Medical UniversityKey Laboratory of Health Ministry for Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital, China Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusion These findings collectively indicate that intra-amniotic transplanted BDNF-BMSCs have an advantage of promoting the recovery of defective neural tissue of SBA fetuses.https://doi.org/10.1186/s13287-022-03105-6Spina bifida apertaMesenchymal stem cells derived from bone marrowBrain-derived neurotrophic factorIntra-amniotic transplantationPrenatal treatment |
| spellingShingle | Wei Ma Xiaowei Wei Hui Gu Dan Liu Wenting Luo Songying Cao Shanshan Jia Yiwen He Lizhu Chen Yuzuo Bai Zhengwei Yuan Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta Stem Cell Research & Therapy Spina bifida aperta Mesenchymal stem cells derived from bone marrow Brain-derived neurotrophic factor Intra-amniotic transplantation Prenatal treatment |
| title | Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| title_full | Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| title_fullStr | Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| title_full_unstemmed | Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| title_short | Intra-amniotic transplantation of brain-derived neurotrophic factor-modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| title_sort | intra amniotic transplantation of brain derived neurotrophic factor modified mesenchymal stem cells treatment for rat fetuses with spina bifida aperta |
| topic | Spina bifida aperta Mesenchymal stem cells derived from bone marrow Brain-derived neurotrophic factor Intra-amniotic transplantation Prenatal treatment |
| url | https://doi.org/10.1186/s13287-022-03105-6 |
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