Intra‐amniotic mesenchymal stem cell therapy improves the amniotic fluid microenvironment in rat spina bifida aperta fetuses

• Published in: Cell proliferation Vol. 56; no. 2; pp. e13354 - n/a
• Main Authors: Wei, Xiaowei, Ma, Wei, Gu, Hui, Liu, Dan, Luo, Wenting, Cao, Songying, Jia, Shanshan, Huang, Tianchu, He, Yiwen, Bai, Yuzuo, Wang, Weilin, Yuan, Zhengwei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2023; John Wiley and Sons Inc
• Subjects: Abdomen; Activin; Amniotic fluid; Amniotic Fluid - metabolism; Animal models; Animals; Apoptosis; Bone marrow; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Cell therapy; Ciliary Neurotrophic Factor - metabolism; Ciliary Neurotrophic Factor - pharmacology; CXCR4 protein; Cytokines; Cytokines - metabolism; Degeneration; Differentiation; Disability; Embryos; Engraftment; Experiments; Fetuses; In vivo methods and tests; Injuries; Laboratory animals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Microenvironments; Nerve growth factor; Neural tube defects; Original; Rats; Recovery of function; Skin; Spina bifida; Spina Bifida Cystica - metabolism; Spina Bifida Cystica - therapy; Stem cells; Surgery; Synaptogenesis; Transplantation; Uterus; United States > US; China
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.13354

Objectives 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. Methods 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. Results 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. Conclusion BMSC transplantation can improve the amniotic fluid environment, and this is beneficial for SBA repair. In utero intra‐amniotic BMSC or PBS microinjection in the E15 fetuses was performed in E15 rat fetuses with spina bifida aperta, and amniotic fluid was collected at E21 for protein array detection. Venn diagram shows the relationship of three biological processes (GO: 0030335, 0048699, and 0043524) and the attribution of differentially expressed proteins. Comparative analysis of five proteins with the largest fold changes in the process of generation of neurons.