Intra-amniotic transplantation of APOM-modified BMSCs facilitates neural repair in spina bifida by improving vascular endothelial integrity.

@article{liu2026intraamniotic,
  title = {{Intra-amniotic transplantation of APOM-modified BMSCs facilitates neural repair in spina bifida by improving vascular endothelial integrity.}},
  author = {Yihui Liu and Ziqi Zhao and Liaoyue Chen and Xiaowei Wei and Dongxue Ding and Songying Cao and Hui Gu and Dan Liu and Lizhu Chen and Shanshan Jia and Wenting Luo and Zhitong Cai and Qinglong Wu and Tianchu Huang and Wanqi Huang and Yiwen He and Jia Xue and Zhengwei Yuan and Wei Ma},
  journal = {Cell communication and signaling : CCS},
  year = {2026},
  month = aug,
  doi = {10.1186/s12964-026-03120-7},
  url = {https://europepmc.org/article/MED/42958406},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Intra-amniotic transplantation of APOM-modified BMSCs facilitates neural repair in spina bifida by improving vascular endothelial integrity.
AU  - Yihui Liu
AU  - Ziqi Zhao
AU  - Liaoyue Chen
AU  - Xiaowei Wei
AU  - Dongxue Ding
AU  - Songying Cao
AU  - Hui Gu
AU  - Dan Liu
AU  - Lizhu Chen
AU  - Shanshan Jia
AU  - Wenting Luo
AU  - Zhitong Cai
AU  - Qinglong Wu
AU  - Tianchu Huang
AU  - Wanqi Huang
AU  - Yiwen He
AU  - Jia Xue
AU  - Zhengwei Yuan
AU  - Wei Ma
PY  - 2026
DA  - 2026/08/01
JO  - Cell communication and signaling : CCS
DO  - 10.1186/s12964-026-03120-7
UR  - https://europepmc.org/article/MED/42958406
AB  - Background  Spina 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  APOM 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  SBA 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  Our 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.
SN  - 1478-811X
ER  -