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A Dual Role of Mesenchymal Stem Cell Derived Small Extracellular Vesicles on TRPC6 Protein and Mitochondria to

Min Wang1,2, Dakai Yang1, Linli Li3

  • 1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Clinical Laboratory, School of Medicine, Jiangsu University, Zhenjiang 212000, China.

ACS Nano
|January 30, 2024
PubMed

Insights

Diabetic wound healing is impaired by calcium dysregulation. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) restore calcium balance by enhancing TRPC6 and mitochondrial function, offering a potential therapeutic strategy.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Wound Healing Research

Background:

  • Diabetic wounds heal poorly due to vascular and nerve damage.
  • Cellular calcium (Ca2+) homeostasis dysregulation is linked to insulin resistance and type 2 diabetes mellitus.
  • The role of calcium dysregulation in diabetic wound complications is not well understood.

Purpose of the Study:

  • Investigate calcium dysregulation in diabetic ulcers.
  • Examine the impact of high glucose on TRPC6 and mitochondria.
  • Evaluate the therapeutic potential of mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) in restoring calcium homeostasis and promoting diabetic wound healing.

Main Methods:

  • Tissue protein profiling of diabetic ulcer patients to identify calcium dysregulation.
  • In vitro stimulation of cells with high glucose and glucometabolic toxicants.
  • Analysis of TRPC6 channel and mitochondrial function.
  • Characterization of MSC-sEV cargo (SP2, USP9) and their effects on target gene expression and cellular processes like mitophagy.

Main Results:

  • Calcium dysregulation was confirmed in patients with diabetic ulcers.
  • High glucose impaired TRPC6 function and mitochondrial health.
  • MSC-sEVs delivered SP2 to activate TRPC6 expression, restoring Ca2+ influx.
  • MSC-sEVs delivered USP9 to stabilize Parkin, promoting mitophagy and restoring mitochondrial function by facilitating Ca2+ efflux.

Conclusions:

  • Targeting calcium homeostasis offers a new perspective on understanding diabetic wound healing.
  • MSC-derived small extracellular vesicles (MSC-sEVs) demonstrate a dual role in restoring TRPC6 and mitochondrial function.
  • Engineered MSC-sEVs represent a promising therapeutic strategy for diabetic wound complications by modulating calcium balance.
Keywords:
TRPC6calcium homeostasisdiabetic wound healinghucMSC-sEVsmitophagy

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