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Human Umbilical Cord Mesenchymal Stem Cells Promote Anti-Inflammation and Angiogenesis by Targeting Macrophages in a Rat Uterine Scar Model

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Abstract

Background

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear.

Methods

Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression.

Results

Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment.

Conclusions

hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors.

Graphical Abstract

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

MSCs:

Mesenchymal stem cells

hUC-MSCs:

Human umbilical cord mesenchymal stem cells

iNOS:

Inducible nitric oxide synthase

IL10:

Interleukin 10

VEGF:

Vascular endothelial growth factor

HOXA10:

Homeobox A10

LIF:

Leukemia inhibitory factor

Arg1:

Arginase 1

TNF-α:

Tumor necrosis factor alpha

PBS:

Phosphate buffer

CS:

Cesarean scar

CSD:

Cesarean scar defect

IUA:

Intrauterine adhesion

PMA:

Phorbol 12-myristate 13-acetate

LPS:

Lipopolysaccharide

IFN-γ:

Interferon gamma

IL4:

Interleukin 4

IL13:

Interleukin 13

HE:

Hematoxylin–eosin

IHC:

Immunohistochemical

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Acknowledgements

We thank the technical help and support from Prof. Jiasong Guo and the medical research center of Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde). Graphical abstract was created in BioRender.com.

Funding

This study was supported by Guangdong Basic and Applied Basic Research Foundation (2019B1515120082), the Science and Technology Bureau of Foshan City (2020001006077, 2020001005230), the Distinguished Young Talents Program of Foshan City (600015), and the scientific research launched project of Shunde Hospital, Southern Medical University (SRSP2021004).

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Qian Yang and Jinfa Huang contributed equally to this work.

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  1. Qian Yang and Jinfa Huang contributed equally to this work.

Authors and Affiliations

  1. Gynecology Department, Shunde Hospital, Southern Medical University, Foshan, 528308, China

    Qian Yang, Jinfa Huang, Yixuan Liu, Qiqing Mai, Yuan Zhou, Lei Zhou, Lingling Zeng & Kaixian Deng

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  1. Qian Yang
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  2. Jinfa Huang
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  3. Yixuan Liu
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Contributions

Q Yang participated in all experiments, in the design of the study and wrote the manuscript. JF Huang was involved in study design, data interpretation, and manuscript composition. YX Liu participated in the animal model establishment and sample collection of partial animal experiments. QQ Mai, Y Zhou, L Zhou, and LL Zeng contributed to data analysis and edited the manuscript. KX Deng conceived of the manuscript’s purpose and design and critically revised the manuscript. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

Corresponding author

Correspondence to Kaixian Deng.

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Ethical treatment of animals used in this study was proposed to and approved by Shunde Hospital, Southern Medical University Ethics Committee (20200731).

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The authors declare no competing interests.

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Yang, Q., Huang, J., Liu, Y. et al. Human Umbilical Cord Mesenchymal Stem Cells Promote Anti-Inflammation and Angiogenesis by Targeting Macrophages in a Rat Uterine Scar Model. Stem Cell Rev and Rep (2024). https://doi.org/10.1007/s12015-024-10730-6

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