A new cell-free therapeutic strategy for liver regeneration: Human placental mesenchymal stem cell-derived extracellular vesicles

Abstract

Mesenchymal stem cells (MSCs) have potential role in organ regeneration therapy. Previous work indicating that MSCs confer protection against liver disease. Here, we aimed to determine the potential application in liver regeneration of human placenta-derived MSCs extracellular vesicles (hPMSCs-EVs) via experimental hepatectomy. hPMSCs-EVs were administered intravenously 24 h before 70% partial hepatectomy, the specific composition of hPMSCs-EVs was identified by sequencing and validated by the quantitative polymerase chain reaction, including circ-RBM23. The role of circ-RBM23 in L02 cell was evaluated and it was found that circ-RBM23 knockdown inhibited L02 cell proliferation both in vitro and in vivo. The competing endogenous RNA function of circ-RBM23 was evaluated by the RNA immunoprecipitation assay and found that circ-RBM23 shares miRNA response elements with RRM2. Overexpressed circ-RBM23 bound competitively to miR-139-5p, preventing the miRNA-mediated degradation of RRM2, activating the expression of eIF4G and AKT/mTOR, and facilitating liver regeneration. These results indicate that hPMSCs-EVs prevent hepatic dysfunction and improve liver regeneration in vivo and hepatocytes proliferation in vitro, potentially via circ-RBM23 delivery.

Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade

“…Jun et al [ 377 ] reported that C-reactive protein in placenta MSCs-derived exosomes triggers hepatic regeneration via the Wnt signaling pathway. Moreover, Li et al [ 378 ] suggested that human placenta PMSCs exosomal circ-RBM23, by sponging miR-139-5p, stimulate cell proliferation and liver regeneration after hepatectomy through the AKT/mTOR pathway. More recently, Chen et al [ 372 ] showed that exosomes derived from hepatocyte-derived liver progenitor-like cells (HepLPCs), could enhance hepatic regeneration after acute liver failure in vivo via the FoxO1/Akt/GSK3β/β-catenin axis.…”

Harnessing Stem Cell-Derived Extracellular Vesicles for the Regeneration of Degenerative Bone Conditions

“…Of note, placental EVs are rich in growth factors and angiogenic factors, making them potential candidates for promoting tissue repair and regeneration in various medical fields, including bone repair and tissue engineering. 57 …”

“…Of note, placental EVs are rich in growth factors and angiogenic factors, making them potential candidates for promoting tissue repair and regeneration in various medical fields, including bone repair and tissue engineering. 57 Compared to the transplantation of MSCs themselves, the utilization of EVs presents a compelling alternative that mitigates certain risks associated with cell-based therapies. Concerns such as unwanted differentiation, immune rejection, and teratoma formation can be effectively decreased by utilizing MSC-derived EVs.…”

Mesenchymal stem cells derived exosomes ameliorate D-galN/LPS induced acute liver injury via PTEN-mediated macrophage polarization

“…Human placental mesenchymal stem cells (hPMSCs) were acquired from Zhujiang Hospital of Southern Medical University, following the previously described isolation and culture methods 23 . Mouse macrophages were maintained in DMEM supplemented with 10% FBS.…”

“…The dual-luciferase assay was performed according to the manufacturer's instructions using the dualluciferase reporter assay kit from Promega (Madison, WI, USA), as described previously 23 . Mouse macrophages were seeded on 24-well plates and cultured until they reached 50% con uence.…”