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

    OnderzoeksoutputAcademicpeer review

    15 Citaten (Scopus)
    205 Downloads (Pure)

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    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.

    Originele taal-2English
    Pagina's (van-tot)107-121
    Aantal pagina's15
    TijdschriftCell reports
    Volume18
    Nummer van het tijdschrift1
    DOI's
    StatusPublished - 3-jan-2017

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