Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorated Insulin Resistance in Type 2 Diabetes Mellitus Rats
Seng Kar Yap,
Kian Leong Tan,
Nor Yasmin Abd Rahaman,
Nur Fazila Saulol Hamid,
Der Jiun Ooi,
Yin Sim Tor,
Qi Hao Daniel Looi,
Li Kar Stella Tan,
Chee Wun How,
Jhi Biau Foo
Affiliations
Seng Kar Yap
Ming Medical Sdn. Bhd., D3-3 (2nd Floor), Block D3, Dana 1 Commercial Centre, Jalan PJU 1A/46, Petaling Jaya 47301, Selangor, Malaysia
Kian Leong Tan
School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Nor Yasmin Abd Rahaman
Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Nur Fazila Saulol Hamid
Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
Der Jiun Ooi
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jenjarum 42610, Selangor, Malaysia
Yin Sim Tor
School of Biosciences, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Qi Hao Daniel Looi
Ming Medical Sdn. Bhd., D3-3 (2nd Floor), Block D3, Dana 1 Commercial Centre, Jalan PJU 1A/46, Petaling Jaya 47301, Selangor, Malaysia
Li Kar Stella Tan
School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Chee Wun How
School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
Jhi Biau Foo
Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Selangor, Malaysia
Human umbilical cord mesenchymal stem cell-derived small extracellular vesicle (hUC-MSCs-sEVs) therapy has shown promising results to treat diabetes mellitus in preclinical studies. However, the dosage of MSCs-sEVs in animal studies, up to 10 mg/kg, was considered high and may be impractical for future clinical application. This study aims to investigate the efficacy of low-dose hUC-MSCs-sEVs treatment on human skeletal muscle cells (HSkMCs) and type 2 diabetes mellitus (T2DM) rats. Treatment with hUC-MSCs-sEVs up to 100 μg/mL for 48 h showed no significant cytotoxicity. Interestingly, 20 μg/mL of hUC-MSCs-sEVs-treated HSkMCs increased glucose uptake by 80–90% compared to untreated cells. The hUC-MSCs-sEVs treatment at 1 mg/kg improved glucose tolerance in T2DM rats and showed a protective effect on complete blood count. Moreover, an improvement in serum HbA1c was observed in diabetic rats treated with 0.5 and 1 mg/kg of hUC-MSCs-sEVs, and hUC-MSCs. The biochemical tests of hUC-MSCs-sEVs treatment groups showed no significant creatinine changes, elevated alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels compared to the normal group. Histological analysis revealed that hUC-MSCs-sEVs relieved the structural damage to the pancreas, kidney and liver. The findings suggest that hUC-MSCs-sEVs could ameliorate insulin resistance and exert protective effects on T2DM rats. Therefore, hUC-MSCs-sEVs could serve as a potential therapy for diabetes mellitus.
