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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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Autores principales: Yap, Seng Kar, Tan, Kian Leong, Abd Rahaman, Nor Yasmin, Saulol Hamid, Nur Fazila, Ooi, Der Jiun, Tor, Yin Sim, Daniel Looi, Qi Hao, Stella Tan, Li Kar, How, Chee Wun, Foo, Jhi Biau
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948940/
https://www.ncbi.nlm.nih.gov/pubmed/35336023
http://dx.doi.org/10.3390/pharmaceutics14030649
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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
Stella Tan, Li Kar
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
Stella Tan, Li Kar
How, Chee Wun
Foo, Jhi Biau
author_sort Yap, Seng Kar
collection PubMed
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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spelling pubmed-89489402022-03-26 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 Stella Tan, Li Kar How, Chee Wun Foo, Jhi Biau Pharmaceutics Article 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. MDPI 2022-03-16 /pmc/articles/PMC8948940/ /pubmed/35336023 http://dx.doi.org/10.3390/pharmaceutics14030649 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yap, Seng Kar
Tan, Kian Leong
Abd Rahaman, Nor Yasmin
Saulol Hamid, Nur Fazila
Ooi, Der Jiun
Tor, Yin Sim
Daniel Looi, Qi Hao
Stella Tan, Li Kar
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948940/
https://www.ncbi.nlm.nih.gov/pubmed/35336023
http://dx.doi.org/10.3390/pharmaceutics14030649
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