Extracellular Vesicles Derived from Type 2 Diabetic Mesenchymal Stem Cells Induce Endothelial Mesenchymal Transition under High Glucose Conditions Through the TGFß/Smad3 Signaling Pathway.
Stem Cells Dev
; 33(11-12): 262-275, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38717965
ABSTRACT
Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, which results in delayed wound healing. Mesenchymal stem cells (MSCs) play a vital role in supporting endothelial cells (ECs) and promoting wound healing by paracrine effects through their secretome-containing extracellular vesicles. We previously reported the impaired wound healing ability of adipose tissue-derived MSC from T2DM donors; however, whether extracellular vesicles isolated from T2DM adipose tissue-derived MSCs (dEVs) exhibit altered functions in comparison to those derived from healthy donors (nEVs) is still unclear. In this study, we found that nEVs induced EC survival and angiogenesis, whereas dEVs lost these abilities. In addition, under high glucose conditions, nEV protected ECs from endothelial-mesenchymal transition (EndMT), whereas dEV significantly induced EndMT by activating the transforming growth factor-ß/Smad3 signaling pathway, which impaired the tube formation and in vivo wound healing abilities of ECs. Interestingly, the treatment of dEV-internalized ECs with nEVs rescued the induced EndMT effects. Of note, the internalization of nEV into T2DM adipose tissue-derived MSC resulted in the production of an altered n-dEV, which inhibited EndMT and supported the survival of T2DM db/db mice from severe wounds. Taken together, our findings suggest the role of dEV in endothelial dysfunction and delayed wound healing in T2DM by the promotion of EndMT. Moreover, nEV treatment can be considered a promising candidate for cell-free therapy to protect ECs in T2DM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Transforming Growth Factor beta
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Endothelial Cells
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Diabetes Mellitus, Type 2
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Smad3 Protein
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Mesenchymal Stem Cells
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Extracellular Vesicles
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Glucose
Limits:
Animals
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Female
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Humans
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Male
Language:
En
Journal:
Stem Cells Dev
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Japan