Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome

Background/Objective: Metabolic syndrome (MetS) is characterized by abdominal obesity, increased blood pressure (BP), fasting blood glucose (FBG) and triglyceride levels, and reduced high-density lipoprotein (HDL) levels. This study aims to investigate the efficacy of the Wharton’s jelly mesenchymal...

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Main Authors: Illayaraja Krishnan, Magdalene Tan Mei Ling, Min Hwei Ng, Jia Xian Law, Mohd Rafizul Mohd Yusof, Thavachelvi Thangarajah, Zalina Mahmood, Nurul Izzati Uda Zahli, Shathiya Rajamanickam, Baskar Subramani, Yogeswaran Lokanathan
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/44
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author Illayaraja Krishnan
Magdalene Tan Mei Ling
Min Hwei Ng
Jia Xian Law
Mohd Rafizul Mohd Yusof
Thavachelvi Thangarajah
Zalina Mahmood
Nurul Izzati Uda Zahli
Shathiya Rajamanickam
Baskar Subramani
Yogeswaran Lokanathan
author_facet Illayaraja Krishnan
Magdalene Tan Mei Ling
Min Hwei Ng
Jia Xian Law
Mohd Rafizul Mohd Yusof
Thavachelvi Thangarajah
Zalina Mahmood
Nurul Izzati Uda Zahli
Shathiya Rajamanickam
Baskar Subramani
Yogeswaran Lokanathan
author_sort Illayaraja Krishnan
collection DOAJ
description Background/Objective: Metabolic syndrome (MetS) is characterized by abdominal obesity, increased blood pressure (BP), fasting blood glucose (FBG) and triglyceride levels, and reduced high-density lipoprotein (HDL) levels. This study aims to investigate the efficacy of the Wharton’s jelly mesenchymal stem cells (WJMSCs)-derived small extracellular vesicles’ (sEVs) preparations in managing MetS. Method: Twenty-four rats were fed with a high-fat and high-fructose diet to induce MetS for 16 weeks and randomized into three groups (<i>n</i> = 8/group): a MetS Control group treated with normal saline, MetS Low Dose (LD) group treated with a LD of sEVs preparations (3 × 10<sup>9</sup> particle/rat), and MetS High Dose (HD) group treated with a HD of sEVs preparations (9 × 10<sup>9</sup> particles/rat). The Control Non-Disease (ND) group was given a standard rat diet and autoclaved tap water with normal saline as treatment. Treatments were given via intravenous injection every three weeks for twelve weeks. Rats were assessed every six weeks for physical measurements, FBG, lipid profiles, CRP, leptin, adiponectin, and BP. Necropsy evaluation was performed on the lungs, liver, spleen, and kidney. Results: Significant reductions in FBG, triglycerides, BP, and increased HDL levels were observed in the treated groups compared to the control group. However, significant abdominal circumference (AC) improvement was not observed in the treated groups. Non-significant associations were found between fasting CRP, leptin, and adiponectin levels with MetS rats after treatment. In addition, sEVs preparations improved inflammation and hemorrhage in the lung and mineralisation in the renal of the treated group. Conclusions: Human fetal WJMSCs-derived sEVs preparations improve all the clusters of MetS in rats except AC and could be further explored as a treatment for MetS.
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spelling doaj-art-ce563c61b2454ac3ae964a5a4511bb712025-01-24T13:24:58ZengMDPI AGBiomolecules2218-273X2025-01-011514410.3390/biom15010044Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic SyndromeIllayaraja Krishnan0Magdalene Tan Mei Ling1Min Hwei Ng2Jia Xian Law3Mohd Rafizul Mohd Yusof4Thavachelvi Thangarajah5Zalina Mahmood6Nurul Izzati Uda Zahli7Shathiya Rajamanickam8Baskar Subramani9Yogeswaran Lokanathan10Department of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaDepartment of Obstetrics and Gynaecology, Hospital Angkatan Tentera (HAT) Tuanku Mizan, Wangsa Maju, Kuala Lumpur 53300, MalaysiaProduction and Blood Supply Management Division, National Blood Centre, Jalan Tun Razak, Kuala Lumpur 50400, MalaysiaDepartment of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang 43400, MalaysiaMedixcell Sdn. Bhd., Level 5, Equatorial Plaza, Lot 5-5 & 5-6, Jalan Sultan Ismail, Kuala Lumpur 50250, MalaysiaMedixcell Sdn. Bhd., Level 5, Equatorial Plaza, Lot 5-5 & 5-6, Jalan Sultan Ismail, Kuala Lumpur 50250, MalaysiaDepartment of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur 56000, MalaysiaBackground/Objective: Metabolic syndrome (MetS) is characterized by abdominal obesity, increased blood pressure (BP), fasting blood glucose (FBG) and triglyceride levels, and reduced high-density lipoprotein (HDL) levels. This study aims to investigate the efficacy of the Wharton’s jelly mesenchymal stem cells (WJMSCs)-derived small extracellular vesicles’ (sEVs) preparations in managing MetS. Method: Twenty-four rats were fed with a high-fat and high-fructose diet to induce MetS for 16 weeks and randomized into three groups (<i>n</i> = 8/group): a MetS Control group treated with normal saline, MetS Low Dose (LD) group treated with a LD of sEVs preparations (3 × 10<sup>9</sup> particle/rat), and MetS High Dose (HD) group treated with a HD of sEVs preparations (9 × 10<sup>9</sup> particles/rat). The Control Non-Disease (ND) group was given a standard rat diet and autoclaved tap water with normal saline as treatment. Treatments were given via intravenous injection every three weeks for twelve weeks. Rats were assessed every six weeks for physical measurements, FBG, lipid profiles, CRP, leptin, adiponectin, and BP. Necropsy evaluation was performed on the lungs, liver, spleen, and kidney. Results: Significant reductions in FBG, triglycerides, BP, and increased HDL levels were observed in the treated groups compared to the control group. However, significant abdominal circumference (AC) improvement was not observed in the treated groups. Non-significant associations were found between fasting CRP, leptin, and adiponectin levels with MetS rats after treatment. In addition, sEVs preparations improved inflammation and hemorrhage in the lung and mineralisation in the renal of the treated group. Conclusions: Human fetal WJMSCs-derived sEVs preparations improve all the clusters of MetS in rats except AC and could be further explored as a treatment for MetS.https://www.mdpi.com/2218-273X/15/1/44umbilical cordexosomesmetabolic diseasessyndrome Xbiotherapeutics
spellingShingle Illayaraja Krishnan
Magdalene Tan Mei Ling
Min Hwei Ng
Jia Xian Law
Mohd Rafizul Mohd Yusof
Thavachelvi Thangarajah
Zalina Mahmood
Nurul Izzati Uda Zahli
Shathiya Rajamanickam
Baskar Subramani
Yogeswaran Lokanathan
Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
Biomolecules
umbilical cord
exosomes
metabolic diseases
syndrome X
biotherapeutics
title Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
title_full Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
title_fullStr Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
title_full_unstemmed Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
title_short Efficacy of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles in Metabolic Syndrome
title_sort efficacy of fetal wharton s jelly mesenchymal stem cells derived small extracellular vesicles in metabolic syndrome
topic umbilical cord
exosomes
metabolic diseases
syndrome X
biotherapeutics
url https://www.mdpi.com/2218-273X/15/1/44
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