PMID- 35336023
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220329
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 3
DP  - 2022 Mar 16
TI  - Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles 
      Ameliorated Insulin Resistance in Type 2 Diabetes Mellitus Rats.
LID - 10.3390/pharmaceutics14030649 [doi]
LID - 649
AB  - 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 mug/mL for 
      48 h showed no significant cytotoxicity. Interestingly, 20 mug/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.
FAU - Yap, Seng Kar
AU  - Yap SK
AUID- ORCID: 0000-0003-3912-1419
AD  - Ming Medical Sdn. Bhd., D3-3 (2nd Floor), Block D3, Dana 1 Commercial Centre, 
      Jalan PJU 1A/46, Petaling Jaya 47301, Selangor, Malaysia.
FAU - Tan, Kian Leong
AU  - Tan KL
AD  - School of Biosciences, Faculty of Health and Medical Sciences, Taylor's 
      University, Subang Jaya 47500, Selangor, Malaysia.
FAU - Abd Rahaman, Nor Yasmin
AU  - Abd Rahaman NY
AD  - Department of Veterinary Pathology and Microbiology, Faculty of Veterinary 
      Medicine, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
FAU - Saulol Hamid, Nur Fazila
AU  - Saulol Hamid NF
AD  - Department of Veterinary Pathology and Microbiology, Faculty of Veterinary 
      Medicine, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
FAU - Ooi, Der Jiun
AU  - Ooi J
AUID- ORCID: 0000-0002-4896-2351
AD  - Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA 
      University, Jenjarum 42610, Selangor, Malaysia.
FAU - Tor, Yin Sim
AU  - Tor YS
AUID- ORCID: 0000-0002-4354-1486
AD  - School of Biosciences, Faculty of Health and Medical Sciences, Taylor's 
      University, Subang Jaya 47500, Selangor, Malaysia.
AD  - Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health 
      and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia.
FAU - Daniel Looi, Qi Hao
AU  - Daniel Looi QH
AD  - Ming Medical Sdn. Bhd., D3-3 (2nd Floor), Block D3, Dana 1 Commercial Centre, 
      Jalan PJU 1A/46, Petaling Jaya 47301, Selangor, Malaysia.
AD  - My Cytohealth Sdn. Bhd., 18-2, Jalan Radin Bagus 1, Bandar Seri Petaling, Kuala 
      Lumpur 57000, Malaysia.
FAU - Stella Tan, Li Kar
AU  - Stella Tan LK
AUID- ORCID: 0000-0002-0238-3995
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, 
      Subang Jaya 47500, Selangor, Malaysia.
FAU - How, Chee Wun
AU  - How CW
AD  - School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Selangor, 
      Malaysia.
FAU - Foo, Jhi Biau
AU  - Foo JB
AD  - Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health 
      and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia.
AD  - School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, 
      Subang Jaya 47500, Selangor, Malaysia.
LA  - eng
GR  - MING/2019/SOP/001/Ming Medical Sdn. Bhd./
PT  - Journal Article
DEP - 20220316
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8948940
OTO - NOTNLM
OT  - exosomes
OT  - insulin resistance
OT  - mesenchymal stem cell
OT  - small extracellular vesicle
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest. My Cytohealth Sdn. Bhd had no role 
      in the design of the study; in the collection, analyses, or interpretation of 
      data; in the writing of the manuscript, or in the decision to publish the 
      results.
EDAT- 2022/03/27 06:00
MHDA- 2022/03/27 06:01
PMCR- 2022/03/16
CRDT- 2022/03/26 01:04
PHST- 2022/02/15 00:00 [received]
PHST- 2022/03/07 00:00 [revised]
PHST- 2022/03/11 00:00 [accepted]
PHST- 2022/03/26 01:04 [entrez]
PHST- 2022/03/27 06:00 [pubmed]
PHST- 2022/03/27 06:01 [medline]
PHST- 2022/03/16 00:00 [pmc-release]
AID - pharmaceutics14030649 [pii]
AID - pharmaceutics-14-00649 [pii]
AID - 10.3390/pharmaceutics14030649 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Mar 16;14(3):649. doi: 10.3390/pharmaceutics14030649.