from 3D-cultured canine adipose-derived stem cells are identified as nanosized vesicles around 72 nm with a high particle concentration of 1.07 × 10^10 particles/mL.
sEVs protected INS-1 β-cells from etoposide-induced damage, enhancing cell viability and reducing apoptosis.
In diabetic mice, sEV treatment significantly improved glycemic control and glucose metabolism.
Improvements were observed in β-cell function as measured by HOMA-β, , and QUICKI indices.
sEVs reduced systemic inflammation and restored immune homeostasis.
Double-dose sEV administration yielded the most pronounced benefits, including enhanced glucose clearance.
Simplified
BACKGROUND: (sEVs) derived from mesenchymal stem cells are emerging as promising therapeutic agents in regenerative medicine. This study evaluated the therapeutic potential of sEVs from 3D-cultured canine adipose-derived mesenchymal stem cells in alleviating diabetes-induced systemic dysfunctions, focusing on their revitalizing, metabolic, and immunomodulatory properties.
RESULTS: sEVs were identified as nanosized vesicles around 72 nm with a negative zeta potential (-21.15 mV) and a high particle concentration (1.07 × 10particles/mL). In vitro, sEVs (10particles/mL) protected INS-1 β-cells from etoposide (ETO)-induced cytotoxicity, enhancing cell viability, reducing apoptosis, and promoting recovery. Biodistribution analysis showed detectable levels in plasma for up to 24 h post-injection, suggesting sustained circulation and a potentially extended half-life compared to free therapeutic molecules. In streptozotocin (STZ)-induced diabetic mice, sEV treatment significantly improved glycemic control, enhanced glucose metabolism, and restored β-cell function, as reflected by improvements in HOMA-β, , and QUICKI indices. Additionally, sEVs reduced systemic inflammation, restored immune homeostasis, and improved hematological, renal, and hepatic parameters. Double-dose sEV administration yielded the most pronounced therapeutic benefits, including enhanced glucose clearance and systemic recovery. 9 4
CONCLUSIONS: sEVs exhibit robust revitalizing, metabolic, and immunomodulatory properties, effectively mitigating diabetes-related dysfunctions in vitro and in vivo. These findings highlight sEVs as a novel regenerative therapy for diabetes and its complications, providing a strong foundation for future clinical translation.
Key numbers
709.00 ± 28.54 mg/dL to 514.10 ± 44.96 mg/dL
Fasting Blood Glucose Reduction
Double-dose group fasting blood glucose levels from Day −1 to Day 21.
0.15 ± 0.006 AU to 0.32 ± 0.08 AU
HOMA-β Improvement
HOMA-β values in single-dose vs. triple-dose groups.
24 h
Systemic Safety
Duration of detectable in plasma post-injection.
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Declarations. Ethics approval and consent to participate: This study adhered to the ARRIVE guidelines and ethical standards established by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Veterinary Science, Chulalongkorn University, Thailand. The research was conducted under two distinct Animal Use Protocols, ensuring compliance with ethical standards and institutional guidelines. Approval for the collection of adipose tissue used in sEV preparation was granted under Animal Use Protocol 2231041. Adipose tissue was collected from a privately owned donor animal with the informed consent of the owner, following ethical procedures for the humane treatment of animals. The biodistribution study and experimental procedures were approved under Animal Use Protocol 2473005. This protocol covered all aspects of animal care and experimental interventions, including acclimatization, intravenous administration of labeled sEVs, blood collection, and organ harvesting. The IACUC operates as an independent entity, ensuring an unbiased and rigorous review process. All experimental processes prioritized animal welfare, adhering strictly to ethical and institutional standards. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
