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Author Spotlight: Advancing Treatment Approaches with Adipose-Derived Stem Cells
Published on: January 12, 2024
Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial
Fengming Zhu1, Octavia L S Chong Lee Shin1, Guangchang Pei1
1Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Abstract:
Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD), however effective treatments are still elusive. This study aimed to investigate the therapeutic efficacy of human adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and illuminate the role of Sox9, a vital transcription factor in the development of kidney, in this process. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment. We found that hAD-MSC treatment upregulated the expression of tubular Sox9, promoted tubular regeneration, attenuated AKI, and mitigated subsequent renal fibrosis. However, these beneficial effects were abolished by a drug inhibiting the release of exosomes from hAD-MSCs. Similarly, Sox9 inhibitors reversed these protective effects. Further, we verified that hAD-MSCs activated tubular Sox9 and prevented TGF-β1-induced transformation of TECs into pro-fibrotic phenotype through exosome shuttling in vitro, but the cells did not inhibit TGF-β1-induced transition of fibroblasts into myofibroblasts. Inhibiting the release of exosomes from hAD-MSCs or the expression of Sox9 in TECs reversed these antifibrotic effects. In conclusion, hAD-MSCs employed exosomes to mitigate AKI-CKD transition through tubular epithelial cell dependent activation of Sox9.
Insights
Human adipose-derived mesenchymal stem cells (hAD-MSCs) prevent chronic kidney disease progression after acute kidney injury. Their exosomes activate Sox9 in kidney tubules, promoting repair and reducing fibrosis.
Area of Science:
- Nephrology
- Regenerative Medicine
- Molecular Biology
Background:
- Acute kidney injury (AKI) significantly increases the risk of developing chronic kidney disease (CKD).
- Effective treatments to prevent the transition from AKI to CKD remain limited.
- Understanding the molecular mechanisms underlying AKI-CKD progression is crucial for developing therapeutic strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of human adipose-derived mesenchymal stem cells (hAD-MSCs) in preventing the AKI-CKD transition.
- To elucidate the role of the transcription factor Sox9 in this process.
- To investigate the involvement of exosomes in hAD-MSC-mediated protection.
Main Methods:
- Unilateral renal ischemia/reperfusion (I/R) injury model in C57BL/6 mice.
- Treatment with hAD-MSCs, exosome inhibitors, or Sox9 inhibitors.
- Assessment of kidney function, tubular regeneration, fibrosis, and gene expression (Sox9).
- In vitro studies using tubular epithelial cells (TECs) and fibroblasts exposed to TGF-β1.
Main Results:
- hAD-MSC treatment attenuated AKI, promoted tubular regeneration, and reduced renal fibrosis.
- These protective effects were dependent on exosome release from hAD-MSCs and Sox9 activation in TECs.
- hAD-MSCs prevented TGF-β1-induced pro-fibrotic transformation of TECs via exosome-mediated Sox9 activation.
- hAD-MSCs did not affect TGF-β1-induced fibroblast activation.
Conclusions:
- hAD-MSCs mitigate the AKI-CKD transition by activating Sox9 in tubular epithelial cells.
- Exosomes secreted by hAD-MSCs play a critical role in delivering therapeutic signals.
- This mechanism highlights a novel therapeutic approach targeting kidney tubule protection to prevent CKD progression.
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