Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration

Elisa Pedone, Vlad-Aris Olteanu, Lucia Marucci, Maria Isabel Munoz-Martin, Sameh A. Youssef, Alain de Bruin, Maria Pia Cosma

    Research output: Contribution to journalArticleAcademicpeer-review

    14 Citations (Scopus)
    203 Downloads (Pure)

    Abstract

    In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection. Here, we find that a block of BMC recruitment into the liver severely impairs its regeneration after the surgery. Mobilized hematopoietic stem and progenitor cells (HSPCs) in the resected liver can fuse with hepatocytes, and the hybrids proliferate earlier than the hepatocytes. Genetic ablation of the hybrids severely impairs hepatocyte proliferation and liver mass regeneration. Mathematical modeling reveals a key role of bone marrow (BM)-derived hybrids to drive proliferation in the regeneration process, and predicts regeneration efficiency in experimentally non-testable conditions. In conclusion, BM-derived hybrids are essential to trigger efficient liver regeneration after hepatectomy.

    Original languageEnglish
    Pages (from-to)107-121
    Number of pages15
    JournalCell reports
    Volume18
    Issue number1
    DOIs
    Publication statusPublished - 3-Jan-2017

    Keywords

    • HEMATOPOIETIC STEM-CELLS
    • PARTIAL-HEPATECTOMY
    • TISSUE REGENERATION
    • SYSTEMS BIOLOGY
    • IN-VIVO
    • HEPATOCYTES
    • FUSION
    • MICE
    • TRANSPLANTATION
    • DIFFERENTIATION

    Cite this