{
  "abstract": "Background\n\nSpina bifida aperta (SBA) is the most common type of neural tube defects. Although advances in fetoscopy have enabled fetal surgery to offer significant advantages over postnatal repair, the therapeutic efficacy for motor function impairment remains limited. Previously, we observed that the expression of apolipoprotein M (APOM)-a protein involved in lipid metabolism and vascular barrier function-was significantly downregulated during the early development of the SBA spinal cord. Given the critical role of vascular function in nerve repair, this study aims to elucidate the vascular pathological features of the SBA spinal cord and explore novel therapeutic strategies.Methods\n\nAPOM expression in SBA fetal spinal cords following the neural tube closure stage until birth was evaluated by Western blotting. Vascular abnormalities and the therapeutic efficacy of intra-amniotic APOM-modified BMSC (APOM-BMSC) transplantation were assessed using Western blotting, immunofluorescence, FITC-Dextran permeability assays and electrophysiological tests. The underlying regulatory mechanism of APOM-BMSCs on endothelial cells was elucidated via cell co-culture, dual-luciferase reporter assays, and ChIP-qPCR. Furthermore, the therapeutic effects of intra-amniotic delivery of APOM-encoding recombinant virus were compared with APOM-BMSC transplantation in rescuing vascular leakage and neural damage.Results\n\nSBA rat fetuses exhibited abnormal vascular development in the spinal cord, characterized by significantly reduced expression of the endothelial tight junction protein ZO1 and increased vascular permeability. Intra-amniotic transplantation of APOM-BMSCs improved vascular endothelial integrity by promoting ZO1 expression. Mechanistically, APOM-BMSCs upregulated endothelial ZO1 expression by inhibiting the overactivation of the NF-κB pathway via S1PR1. In this process, p65 exerts a negative transcriptional regulatory effect on ZO1. Intra-amniotic APOM-BMSC transplantation demonstrated superior efficacy to APOM-overexpressing virus in promoting the recovery of neural injury in SBA rat fetuses.Conclusions\n\nOur findings indicate that spinal vascular abnormalities accompany neural damage in SBA rat fetuses, and intra-amniotic transplantation of APOM-BMSCs may hold potential as a promising therapeutic strategy for restoring vascular integrity and promoting neural repair.",
  "abstract_shown": true,
  "affiliations": [
    "NHC Key Laboratory of Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, Liaoning, 110004, China.",
    "Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.",
    "NHC Key Laboratory of Congenital Malformation, Department of Pediatric Surgery, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, Liaoning, 110004, China. cmu92294183@126.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yihui Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziqi Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Liaoyue Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaowei Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongxue Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Songying Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Lizhu Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanshan Jia"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenting Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhitong Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Qinglong Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianchu Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wanqi Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiwen He"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhengwei Yuan"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Ma",
      "orcid": "0000-0002-7362-6261"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4vagkem6xrdh9.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03120-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13718080",
  "id": "4vagkem6xrdh9",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958406",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2739|Spinal Dysraphism and Malformations"
    ]
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  "openalex": "W7172009281",
  "pdf_url": "https://europepmc.org/articles/PMC13718080?pdf=render",
  "pmcid": "PMC13718080",
  "pmid": "42958406",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/4vagkem6xrdh9.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42958406",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958406"
    },
    {
      "first_seen": "2026-11-02T12:22:13Z",
      "native_id": "PMC13718080",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03120-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Spinal Dysraphism and Malformations",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Intra-amniotic transplantation of APOM-modified BMSCs facilitates neural repair in spina bifida by improving vascular endothelial integrity.",
  "title_text": "Intra-amniotic transplantation of APOM-modified BMSCs facilitates neural repair in spina bifida by improving vascular endothelial integrity.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:13Z",
  "url": "https://research.draconitic.com/paper/4vagkem6xrdh9",
  "venue": "Cell communication and signaling : CCS",
  "versions": []
}