Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats

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 fut...

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Main Authors: Yap, Seng Kar, Tan, Kian Leong, Abd Rahaman, Nor Yasmin, Saulol Hamid, Nur Fazila, Ooi, Der Jiun, Tor, Yin Sim, Daniel Looi, Qi Hao, Li, Kar Stella Tan, How, Chee Wun, Foo, Jhi Biau
Format: Article
Published: Multidisciplinary Digital Publishing Institute 2022
Online Access:http://psasir.upm.edu.my/id/eprint/101745/
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author Yap, Seng Kar
Tan, Kian Leong
Abd Rahaman, Nor Yasmin
Saulol Hamid, Nur Fazila
Ooi, Der Jiun
Tor, Yin Sim
Daniel Looi, Qi Hao
Li, Kar Stella Tan
How, Chee Wun
Foo, Jhi Biau
author_facet Yap, Seng Kar
Tan, Kian Leong
Abd Rahaman, Nor Yasmin
Saulol Hamid, Nur Fazila
Ooi, Der Jiun
Tor, Yin Sim
Daniel Looi, Qi Hao
Li, Kar Stella Tan
How, Chee Wun
Foo, Jhi Biau
author_sort Yap, Seng Kar
building UPM Institutional Repository
collection Online Access
description 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.
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institution Universiti Putra Malaysia
institution_category Local University
last_indexed 2025-11-15T13:35:50Z
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spelling upm-1017452023-06-16T20:18:49Z http://psasir.upm.edu.my/id/eprint/101745/ Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats Yap, Seng Kar Tan, Kian Leong Abd Rahaman, Nor Yasmin Saulol Hamid, Nur Fazila Ooi, Der Jiun Tor, Yin Sim Daniel Looi, Qi Hao Li, Kar Stella Tan How, Chee Wun Foo, Jhi Biau 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. Multidisciplinary Digital Publishing Institute 2022-03-16 Article PeerReviewed Yap, Seng Kar and Tan, Kian Leong and Abd Rahaman, Nor Yasmin and Saulol Hamid, Nur Fazila and Ooi, Der Jiun and Tor, Yin Sim and Daniel Looi, Qi Hao and Li, Kar Stella Tan and How, Chee Wun and Foo, Jhi Biau (2022) Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats. Pharmaceutics, 14 (3). art. no. 649. pp. 1-21. ISSN 1999-4923 https://www.mdpi.com/1999-4923/14/3/649 10.3390/pharmaceutics14030649
spellingShingle Yap, Seng Kar
Tan, Kian Leong
Abd Rahaman, Nor Yasmin
Saulol Hamid, Nur Fazila
Ooi, Der Jiun
Tor, Yin Sim
Daniel Looi, Qi Hao
Li, Kar Stella Tan
How, Chee Wun
Foo, Jhi Biau
Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title_full Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title_fullStr Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title_full_unstemmed Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title_short Human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
title_sort human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorated insulin resistance in type 2 diabetes mellitus rats
url http://psasir.upm.edu.my/id/eprint/101745/
http://psasir.upm.edu.my/id/eprint/101745/
http://psasir.upm.edu.my/id/eprint/101745/