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Impact of repeated intravenous infusions of umbilical cord–derived versus bone marrow–derived mesenchymal stem cells on angiogenesis in a pregnant experimentally induced deep venous thrombosis rat model

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Abstract

Deep venous thrombosis (DVT) therapy during pregnancy warrants special consideration for the woman and the fetus. This study aimed to evaluate the impact of umbilical cord–derived mesenchymal stem cells (UC-MSCs) and bone marrow–derived mesenchymal stem cells (BM-MSCs) in terms of pro-angiogenic capacity and amelioration of pregnancy outcomes. The pregnant DVT rat model was successfully established by the “stenosis” method. Three consecutive injections of both UC-MSCs and BM-MSCs improved angiogenesis and ameliorated the embryo absorption rate in pregnant SD rats with DVT, in which UC-MSCs promoted angiogenesis more significantly. Furthermore, the levels of serum vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor (EGF) were significantly higher in the UC-MSC group compared to those of the BM-MSC group. Thereafter, differentially expressed genes (DEGs) in thrombosed inferior vena cava tissues in the UC-MSC and BM-MSC groups were identified using transcriptome sequencing and further assessed by RT-qPCR and western blotting. The bioinformatics analysis indicated that the enriched DEG terms occurred in the cytokine activity, and the DEG pathways were significantly enriched in the cytokine-cytokine receptor interaction. In addition, both the mRNA and protein levels of angiogenic genes and their receptors, including VEGF-A, VEGF receptor-1, EGF, and EGF receptor, were significantly higher in the UC-MSC group. In conclusion, the BM-MSCs and UC-MSCs both significantly stimulate angiogenesis and ameliorate the embryo absorption rate in pregnant SD rats with DVT, but the difference in cytokine secretion causes UC-MSCs to have more potent angiogenic effects than BM-MSCs.

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Funding

This work was supported by the Scientific Research Project of Jiangsu Provincial Health Committee (Grant No. Z2019003), the Nantong Science and Technology Plan Project (MS12021003), and the Postgraduate Research and Practice Innovation Program of Jiangsu Province (Grant Nos. KYCX20_2799, KYCX21_3118).

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Author notes

  1. Xi Cheng, Weina Wang, and Rong Du contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China

    Xi Cheng, Weina Wang, Rong Du, Yuanyuan Xie, Jingjing Ji & Yuquan Zhang

  2. Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Mu Zhang

  3. Department of Orthopedics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China

    Weiwei Sun

  4. Department of Laboratory, Affiliated Hospital of Nantong University, No. 20 Xi-Si Road, Nantong, 226001, Jiangsu, China

    Baolan Sun

Authors
  1. Xi Cheng
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  2. Weina Wang
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  4. Mu Zhang
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Corresponding authors

Correspondence to Baolan Sun or Yuquan Zhang.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 18 KB) Table S1. RT-qPCR primers for mRNAs.

Supplementary file2 (DOC 901 KB) Table S2. DEGs with cutoff of |log2(fold change)| > 1 and Padj < 0.05.

11626_2022_733_Fig8_ESM.png

Figure S1. Rat DVT model diagram (stenosis). (A) A 2-cm incision in the middle of the abdomen and full exposure and separation of the inferior vena cava branches below the left renal vein to the level of iliac vein. (B) Ligation of the visible branches one by one with 5-0 silk suture. (C) Placement of 5-0 silk suture tightly around the IVC together with 4-0 silk suture. (D) Ligation of IVC and removal of 4-0 silk suture.

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Cheng, X., Wang, W., Du, R. et al. Impact of repeated intravenous infusions of umbilical cord–derived versus bone marrow–derived mesenchymal stem cells on angiogenesis in a pregnant experimentally induced deep venous thrombosis rat model. In Vitro Cell.Dev.Biol.-Animal 58, 957–969 (2022). https://doi.org/10.1007/s11626-022-00733-3

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