Background : Exosomes, extracellular vesicles facilitating intercellular communication, have gained attention as a promising treatment for liver diseases. Recent research highlights the effectiveness of exosomes derived from stem cells, renowned for therapeutic efficacy in liver conditions, sparking a growing interest in exosome-based treatments. A prior study successfully developed chemically derived human hepatic progenitor cells (hCdHs) through direct lineage reprogramming from human hepatocytes, showcasing their ability to regenerate the liver in disease-model mice following transplantation.

Methods : This study focuses on investigating the liver regenerative potential of hCdHs-derived exosomes. hCdHs were cultured on a large scale and exosomes were isolated from the culture supernatant through Ultra-centrifugation. Characterization of the exosomes was conducted through NTA, Western blotting, Flow cytometry, and Cryo-TEM analyses, used in both in vivo and in vitro experiments. Liver disease induction in mice using CCl4 was followed by the intravenous injection of hCdHs-derived exosomes, and the extent of liver damage mitigation was evaluated through H&E, Sirius red, and IHC analyses.

Results : The size and morphology of hCdHs-derived exosomes were assessed using NTA and Cryo-TEM. Confirmation of exosome marker proteins, including CD9, CD63, and CD81, was achieved through Western blotting and Flow cytometry analyses. When these exosomes were injected into mice with liver damage induced by CCl4, liver damage was observed to be alleviated.

Conclusions : As hCdHs-derived exosomes were isolated from patient-specific liver stem cells, it appears that exosomes, along with hCdHs cells, can develop into one of the methods to safely restore liver damage to patients.