Working Paper Article Version 1 This version is not peer-reviewed

Dynamic Regulation of miRNA Expression by Functionally Enhanced Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Rat Model with Bile Duct Ligation

Version 1 : Received: 30 June 2019 / Approved: 1 July 2019 / Online: 1 July 2019 (17:00:18 CEST)

How to cite: Kim, J.Y.; Jun, J.H.; Park, S.Y.; Yang, S.W.; Bae, S.H.; Kim, G.J. Dynamic Regulation of miRNA Expression by Functionally Enhanced Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Rat Model with Bile Duct Ligation. Preprints 2019, 2019070024 Kim, J.Y.; Jun, J.H.; Park, S.Y.; Yang, S.W.; Bae, S.H.; Kim, G.J. Dynamic Regulation of miRNA Expression by Functionally Enhanced Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Rat Model with Bile Duct Ligation. Preprints 2019, 2019070024

Abstract

Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs) were mediated one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with invaded naïve PD-MSCs, invaded PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through RHO family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in PDGFRA by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSCs transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating IL-6 signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem cell therapy in liver diseases.

Subject Areas

liver failure; microRNAs (miRNAs); placenta-derived mesenchymal stem cells (PD-MSCs); phosphatase of regenerating liver-1 (PRL-1); regenerative medicine; stem cells homing; vascular remodeling

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