Tissue Eng Regen Med.  2023 Apr;20(2):295-308. 10.1007/s13770-022-00513-w.

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

• Fu S
• Zhang H
• Li X
• Zhang Q
• Guo C
• Qiu K
• Feng J
• Liu X
• Liu D

• KMID: 2541494
• DOI: http://doi.org/10.1007/s13770-022-00513-w

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.

Keyword

Mesenchymal stem cells; Amniotic membrane; Exosomes; LncRNAs; Angiogenesis