In this study, the authors demonstrated remarkable increases in the numbers and sizes of Small hepatocyte-like progenitor cells (SHPCs) in Ret/PH-treated rat livers that received Bone marrow-derived mesenchymal cells (BM-MC) transplantation or were administered BM-MCs-derived extracellular vesicles (EVs). Additionally, they identified miR-146a-5pthat might play a major role in the growth of Liver stem/progenitor cells (LSPCs), which is a different mechanism other than IL-17RB signaling.
To investigate the transplanted cells, clusters of SHPCs in the recipient’s livers were collected by using laser microdissection (LMD). 7 μm-thick frozen sections were prepared from liver tissues and stained with hematoxylin. The clusters of SHPCs were cut under microscopic observation using the MMI CellCut laser microdissection system. The gene expression patterns in the cells were analyzed using an oligo microarray.
In the present study, the authors demonstrated that the microRNA miR-146a-5p contained in the EVs secreted by BM-MCs plays an important role in the emergence and the expansion of SHPCs. Also, the fact that the enhanced expression of miR-146a-5p in BM-MCs could increase the number of SHPCs may have a possibility to awake the dormant progenitors in severely damaged livers. This finding may provide a valuable clue to facilitate the development of therapeutics for severe liver diseases based on the administration of EVs or their contents, including microRNAs, rather than transplantation with BM-MCs. Further experiments must be performed to elucidate whether the transduction of miR-146a-5p into livers can activate intrinsic hepatocytic progenitor cells and whether unhealthy hepatocytes can be replaced with regenerated hepatocytes.
Read the full publication here:
Ichinohe, N., Ishii, M., Tanimizu, N. et al. Extracellular vesicles containing miR-146a-5p secreted by bone marrow mesenchymal cells activate hepatocytic progenitors in regenerating rat livers. Stem Cell Res Ther 12, 312 (2021). https://doi.org/10.1186/s13287-021-02387-6