Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC

El-Magd, Mohammed A.; Mohamed, Yasser; El‐Shetry, Eman S.; Elsayed, Shafika A.; Gazia, Maha Abo; Abdel-Aleem, Ghada A.; Shafik, Noha M.; Abdo, Walied; El-Desouki, Nabila I.; Basyony, Mohamed A.

doi:10.1016/j.biopha.2019.108732

Cited by 48 publications

(52 citation statements)

References 61 publications

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“…DEN elevated gene expression of CLOCK and BMAL1 , and decreased expression of PER1 , PER2 , and CRY1 , but melatonin injection inhibited these gene expression changes . Another study analyzed the efficacy of the combination of stem cell therapy and melatonin administration in DEN rat models . Although both transplantation of bone marrow‐derived MSCs isolated from young rats as well as melatonin administration (20 mg/kg, twice a week for 5 weeks, i.p.…”

Section: Functional Roles and Therapeutic Potentials Of Melatonin Andmentioning

confidence: 99%

“…85 Another study analyzed the efficacy of the combination of stem cell therapy and melatonin administration in DEN rat models. 86 Although both transplantation of bone marrow-derived MSCs isolated from young rats as well as melatonin administration (20 mg/kg, twice a week for 5 weeks, i.p. injection) attenuated DENinduced liver damage and HCC development in rat liver, the combination of stem cell transplantation and melatonin administration had the highest therapeutic effects by decreasing expression of anti-apoptosis genes including B-cell lymphoma 2 (Bcl-2) and survivin and by increasing apoptotic gene expression such as caspase3 and Bcl-2-associated X protein (BAX) in this model.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

“…injection) attenuated DENinduced liver damage and HCC development in rat liver, the combination of stem cell transplantation and melatonin administration had the highest therapeutic effects by decreasing expression of anti-apoptosis genes including B-cell lymphoma 2 (Bcl-2) and survivin and by increasing apoptotic gene expression such as caspase3 and Bcl-2-associated X protein (BAX) in this model. 86 Chemotherapy is commonly performed especially for advanced HCC, and sorafenib has been widely utilized as the standard agent. 87 Sorafenib treatment induced apoptosis by decreasing the Bcl-2/BAX ratio as well as ER stress followed by autophagy via activation of protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) pathways in HepG2 cells 88 1.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

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Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

Sato

Meng

Francis

et al. 2020

Journal of Pineal Research

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Circadian rhythms and clock gene expressions are regulated by the suprachiasmatic nucleus in the hypothalamus, and melatonin is produced in the pineal gland. Although the brain detects the light through retinas and regulates rhythms and melatonin secretion throughout the body, the liver has independent circadian rhythms and expressions as well as melatonin production. Previous studies indicate the association between circadian rhythms with various liver diseases, and disruption of rhythms or clock gene expression may promote liver steatosis, inflammation, or cancer development. It is well known that melatonin has strong antioxidant effects. Alcohol drinking or excess fatty acid accumulation produces reactive oxygen species and oxidative stress in the liver leading to liver injuries. Melatonin administration protects these oxidative stress‐induced liver damage and improves liver conditions. Recent studies have demonstrated that melatonin administration is not limited to antioxidant effects and it has various other effects contributing to the management of liver conditions. Accumulating evidence suggests that restoring circadian rhythms or expressions as well as melatonin supplementation may be promising therapeutic strategies for liver diseases. This review summarizes recent findings for the functional roles and therapeutic potentials of circadian rhythms and melatonin in liver diseases.

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Section: Functional Roles and Therapeutic Potentials Of Melatonin Andmentioning

confidence: 99%

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Section: Hepatocellular Carcinomamentioning

confidence: 99%

See 1 more Smart Citation

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

Sato

Meng

Francis

et al. 2020

Journal of Pineal Research

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“…The main drawbacks of MSCs therapy are the early pulmonary entrapment and the lack of speci c homing after systemic infusion. Most of the MSCs undergo cell death after transplantation, mainly due to an adverse microenvironment, directly affecting the therapeutic e cacy of MSCs [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…The main drawbacks of MSCs therapy are early pulmonary entrapment and the lack of speci c homing to target tissues following systemic infusion [12,13]. Even when the MSCs reach the target organ, many of the cells undergo apoptosis mainly due to the inhospitable local microenvironmental conditions, such as hypoxia, oxidative stress, and in ammation, which directly affect the therapeutic e cacy of MSCs [14,15]. Application of pretreated MSCs is a novel strategy to enhance the capacity of MSCs to migrate and promote tissue repair in AKI [16,17].…”

Section: Introductionmentioning

confidence: 99%

Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

Zhou

Qiao

Liu

et al. 2020

Preprint

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Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

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The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma

Zhang

Zhu

et al. 2022

Cancer Medicine

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Primary liver cancer is the seventh most common cancer and the second most common cause of cancer death in the world. 1 Globally, hepatocellular carcinoma (HCC) is the main histological type of liver cancer, accounting for more than 75% of the total number of liver cancers. 2 Liver cancer stem cells (LCSCs), recognized by certain surface markers, are responsible for the tumorigenesis, recurrence, metastasis, chemotherapy resistance and poor prognosis of HCC. 3 Increasing evidence supports the great effects of the tumor microenvironment (TME) on the generation, development and metastasis of HCC. TME is composed of diversified cells and non-cellular components. 4 Mesenchymal stem cells (MSCs), an integral part of TME, are considered to be a key factor in tumor progression and metastasis. MSCs are also referred to as "mesenchymal stromal cells", which can further be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and other cells in vitro. 5 Recently, massive research has been devoted to exploring the association between HCC and MSCs. The function of

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Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC

Cited by 48 publications

References 61 publications

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

Melatonin and circadian rhythms in liver diseases: Functional roles and potential therapies

Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

The role of mesenchymal stem cells in the occurrence, development, and therapy of hepatocellular carcinoma

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