PMID- 37031771
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230517
IS  - 1878-5492 (Electronic)
IS  - 0966-3274 (Linking)
VI  - 78
DP  - 2023 Jun
TI  - Curcumin preconditioned mesenchymal stem cells derived exosomes transplantation 
      ameliorate and protect against non- alcoholic steatohepatitis by regulation the 
      expression of key genes of inflammation and oxidative stress.
PG  - 101837
LID - S0966-3274(23)00054-0 [pii]
LID - 10.1016/j.trim.2023.101837 [doi]
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) derived exosomes (MSCs/Exo) is 
      considered a new strategy in cell free regenerative therapy. Curcumin 
      preconditioning of MSCs reported to improve the anti- inflammatory and 
      immunomodulatory properties of MSCs. We investigated the efficacy of exosome 
      (Exo) obtained from curcumin-preconditioned MSCs (MSCs/Exo-Cur) vs. MSC/Exo 
      without curcumin to ameliorate and prevent recurrence of non-alcoholic fatty 
      liver (NASH) disease. METHODS AND RESULTS: In-vivo, methionine/choline-deficient 
      diet (MCD) induced mice non-alcoholic fatty liver disease (NASH) were injected 
      with MSCs/Exo without curcumin or MSCs/Exo-Cur with curcumin. We found that mice 
      treated with MSCs/Exo-Cur had significantly ameliorated steatosis, inflammation, 
      as evaluated by the reduced fibrosis in histopathological examination, decreased 
      the serum level of liver enzymes (p < 0.001), liver triglycerides (TG) 
      (p < 0.001) and cholesterol (Ch) (p < 0.001) and increased the lipid peroxidation 
      (p < 0.001) compared to MSCs/Exo-treated mice. These effects remained for 
      3 months after treatment in MSCs/Exo-Cur-treated mice while features of NASH 
      returned in MSCs/Exo-treated group. In vitro, HepG2 cells were cultured with 
      palmitic acid (PA) and treated with MSCs/Exo or MSCs/Exo-Cur: the MSCs/Exo-Cur 
      exposure reversed the lipotoxic effect from 4.5 to 1.7 fold vs 4.0 fold in 
      MSCs/Exo and oxidative stress in PA-treated HepG2 cells (p < 0.001). We found 
      that MSCs/Exo-Cur regulated the key markers of inflammatory and oxidative stress, 
      genes responsible for fibrogenesis of the liver, key genes of lipid synthesis and 
      transport. Interestingly, MSCs/Exo-Cur significantly down regulated the 
      ASK-JNK-BAX genes involved in mitochondrial stress and apoptosis compared to 
      MSCs/Exo (p < 0.001). CONCLUSION: Our study indicated that exosomes derived from 
      curcumin preconditioned MSCs were able to ameliorate and protect against 
      recurrence of NASH and regulated inflammatory, oxidative stress and 
      mitochondrial-dependent apoptosis ASK-JNK-BAX genes.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Tawfeek, Gehan Abd-Elfatah
AU  - Tawfeek GA
AD  - Clinical Pathology Department Faculty of Medicine, Menoufia University, Egypt. 
      Electronic address: dr.gehansh7977@gmail.com.
FAU - Kasem, Hend Ahmed
AU  - Kasem HA
AD  - Pathology Department, Faculty of Medicine, Menoufia University, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20230407
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - IT942ZTH98 (Curcumin)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Non-alcoholic Fatty Liver Disease/therapy/metabolism
MH  - *Curcumin/therapeutic use/metabolism/pharmacology
MH  - *Exosomes/metabolism
MH  - *Fatty Liver, Alcoholic/metabolism
MH  - bcl-2-Associated X Protein/metabolism
MH  - Inflammation/therapy/metabolism
MH  - *Mesenchymal Stem Cells
MH  - Oxidative Stress
OTO - NOTNLM
OT  - Ameliorative and protective effect
OT  - Curcumin
OT  - Gene regulation
OT  - Mesenchymal stem cells derived exosomes (MSCs/Exo)
OT  - NASH
COIS- Declaration of Competing Interest None.
EDAT- 2023/04/10 06:00
MHDA- 2023/05/15 06:42
CRDT- 2023/04/09 19:23
PHST- 2022/12/13 00:00 [received]
PHST- 2023/04/02 00:00 [revised]
PHST- 2023/04/05 00:00 [accepted]
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/04/10 06:00 [pubmed]
PHST- 2023/04/09 19:23 [entrez]
AID - S0966-3274(23)00054-0 [pii]
AID - 10.1016/j.trim.2023.101837 [doi]
PST - ppublish
SO  - Transpl Immunol. 2023 Jun;78:101837. doi: 10.1016/j.trim.2023.101837. Epub 2023 
      Apr 7.