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Exosomes Derived from Human Amniotic Mesenchymal Stem Cells Facilitate Diabetic Wound Healing by Angiogenesis and Enrich Multiple lncRNAs

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Diabetic wound healing remains a major challenge due to the impaired functionality of angiogenesis by persistent hyperglycemia. Mesenchymal stem cell exosomes are appropriate candidates for regulating the formation of angiogenesis in tissue repair and regeneration. Here, we explored the effects of exosomes derived from human amniotic mesenchymal stem cell (hAMSC-Exos) on the biological activities of human umbilical vein endothelial cells (HUVECs) treated with high glucose and on diabetic wound healing and investigate lncRNAs related to angiogenesis in hAMSC-Exos.

Methods:

hAMSCs and hAMSC-Exos were isolated and identified by flow cytometry or western blot. A series of functional assays such as cell counting kit-8, scratching, transwell and tube formation assays were performed to evaluate the potential effect of hAMSC-Exos on high glucose-treated HUVECs. The effect of hAMSC-Exos on diabetic wound healing were tested by measuring wound closure rates and immunohistochemical staining of CD31. Subsequently, the lncRNAs profiles in hAMSC-Exos and hAMSCs were examined to screen the lncRNAs related to angiogenesis.

Results:

The isolated hAMSC-Exos had a size range of 30–150 nm and were positive for CD9, CD63 and CD81. The hAMSC-Exos facilitate the functional properties of high glucose-treated HUVECs including the proliferation, migration and the angiogenic activities as well as wound closure and angiogenesis in diabetic wound. hAMSC-Exos were enriched lncRNAs that related to angiogenesis, including PANTR1, H19, OIP5-AS1 and NR2F1-AS1.

Conclusion:

Our findings demonstrated hAMSC-Exos facilitate diabetic wound healing by angiogenesis and contain several exosomal lncRNAs related to angiogenesis, which may represent a promising strategy for diabetic wound healing.

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Acknowledgement

This work was supported by the National Natural Science Foundation of China (Grant No. 81460293).

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Author notes

  1. Shangfeng Fu, Hongyan Zhang have contributed equally to this work.

Authors and Affiliations

  1. Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 330006, Jiangxi, People’s Republic of China

    Shangfeng Fu, Hongyan Zhang, Xiancai Li, Chunyan Guo, Keqing Qiu, Junyun Feng, Xiaoxiao Liu & Dewu Liu

  2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Qiling Zhang

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Ethical statement

This study approved by the Medical Research Ethics Committees of the First Affiliated Hospital of Nanchang University (no. 20218-008) and the written informed consents were signed by the pregnant women or their legal guardians.

The animal experiment were approved by the Experimental Animal Welfare Ethics Committee of the First Affiliated Hospital of Nanchang University (Jiangxi, China) (CDYFY-IACUC-202208QR040).

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Supplementary file 1 (DOCX 229 kb)

13770_2022_513_MOESM2_ESM.docx

Supplemental Fig. 1. A Flow cytometry analysis of the CD44, CD73, CD90, CD105, CD34, CD45 and HLA-DR expressions in hAMSCs. Blue lines represent the isotype control, and red lines represent the level of surface markers. B and C The differentiation potential of hAMSCs. The hAMSCs could be induced to differentiate into osteocytes and adipocytes with osteogenic and adipogenic differentiation medium, respectively, and the hAMSCs were stained with Alizarin Red S and Oil Red O after osteocytes and adipocytes differentiated (DOCX 734 kb)

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Fu, S., Zhang, H., Li, X. et al. Exosomes Derived from Human Amniotic Mesenchymal Stem Cells Facilitate Diabetic Wound Healing by Angiogenesis and Enrich Multiple lncRNAs. Tissue Eng Regen Med 20, 295–308 (2023). https://doi.org/10.1007/s13770-022-00513-w

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