Resveratrol improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells in rats with severe acute pancreatitis

Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation.Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was also analyzed.Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05).Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.

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Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

10.21203/rs.3.rs-34046/v1 ◽

2020 ◽

Author(s):

Guodong Song ◽

Jia Zhou ◽

Ruimei Song ◽

Dalu Liu ◽

Weidi Yu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Long Noncoding Rna ◽

Therapeutic Efficacy ◽

Noncoding Rna ◽

Sodium Taurocholate ◽

High Morbidity

Abstract Background: Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP.Methods: MSCs transfected with LncRNA H19 overexpression and knock down plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.Results: Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation.Conclusions: In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

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Bone marrow-derived mesenchymal stem cells alleviate severe acute pancreatitis-induced multiple-organ injury in rats via suppression of autophagy

Experimental Cell Research ◽

10.1016/j.yexcr.2019.111674 ◽

2019 ◽

Vol 385 (2) ◽

pp. 111674 ◽

Cited By ~ 1

Author(s):

Guodong Song ◽

Dalu Liu ◽

Xiang Geng ◽

Zhilong Ma ◽

Yuxiang Wang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Multiple Organ ◽

Organ Injury ◽

Multiple Organ Injury

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Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01940-z ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Guodong Song ◽

Jia Zhou ◽

Ruimei Song ◽

Dalu Liu ◽

Weidi Yu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Long Noncoding Rna ◽

Therapeutic Efficacy ◽

Noncoding Rna ◽

Sodium Taurocholate ◽

High Morbidity

Abstract Background Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP. Methods MSCs transfected with LncRNA H19 overexpression and knockdown plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP. Results Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation. Conclusions In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

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