Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorated Insulin Resistance in Type 2 Diabetes Mellitus Rats

被引：40

作者：

Yap, Seng Kar ^{[1
]}

Tan, Kian Leong ^{[2
]}

Abd Rahaman, Nor Yasmin ^{[3
]}

Hamid, Nur Fazila Saulol ^{[3
]}

Ooi, Der Jiun ^{[4
]}

Tor, Yin Sim ^{[2
,5
]}

Looi, Qi Hao Daniel ^{[1
,6
]}

Tan, Li Kar Stella ^{[7
]}

How, Chee Wun ^{[8
]}

Foo, Jhi Biau ^{[5
,7
]}

机构：

[1] Ming Med Sdn Bhd, D3-3 2nd Floor,Block D3,Dana 1 Commercial Ctr, Petaling Jaya 47301, Selangor, Malaysia

[2] Taylors Univ, Fac Hlth & Med Sci, Sch Biosci, Subang Jaya 47500, Selangor, Malaysia

[3] Univ Putra Malaysia, Fac Vet Med, Dept Vet Pathol & Microbiol, Serdang 43400, Selangor, Malaysia

[4] MAHSA Univ, Fac Dent, Dept Oral Biol & Biomed Sci, Jenjarum 42610, Selangor, Malaysia

[5] Taylors Univ, Fac Hlth & Med Sci, Ctr Drug Discovery & Mol Pharmacol CDDMP, Subang Jaya 47500, Selangor, Malaysia

[6] My Cytohlth Sdn Bhd, 18-2,Jalan Radin Bagus 1, Kuala Lumpur 57000, Malaysia

[7] Taylors Univ, Fac Hlth & Med Sci, Sch Pharm, Subang Jaya 47500, Selangor, Malaysia

[8] Monash Univ Malaysia, Sch Pharm, Bandar Sunway 47500, Selangor, Malaysia

来源：

PHARMACEUTICS | 2022年 / 14卷 / 03期

关键词：

small extracellular vesicle; exosomes; mesenchymal stem cell; type 2 diabetes mellitus; insulin resistance; CYTOCHALASIN B; LIVER; INHIBITION; GLUCOSE; GLUT1;

D O I：

10.3390/pharmaceutics14030649

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 mu g/mL for 48 h showed no significant cytotoxicity. Interestingly, 20 mu g/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.

引用

页数：21

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