Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis.

Abstract

BACKGROUND:

Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing.

RESULTS:

We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing.

CONCLUSIONS:

PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.

• Authors: Yiqiang Hu, Ranyang Tao, Lang Chen, Yuan Xiong, Hang Xue, Liangcong Hu, Chenchen Yan, Xudong Xie, Ze Lin, Adriana C Panayi, Bobin Mi, Guohui Liu
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 19 Issue 1 Pg. 150 (May 21 2021) ISSN: 1477-3155 [Electronic] England
• PMID: 34020670 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inducing Agents
• Collagen
• Pioglitazone

Topics

• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Collagen (metabolism)
• Diabetes Mellitus (metabolism)
• Diabetes Mellitus, Experimental
• Exosomes (metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Male
• Mesenchymal Stem Cells (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Pioglitazone (metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Skin (drug effects)
• Wound Healing (drug effects)