Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration
Elisa Pedone1, Vlad-Aris Olteanu2, Lucia Marucci3
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr Aiguader 88, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
Cell Reports
|January 5, 2017
Summary
Bone marrow cells are crucial for liver regeneration after surgery. These cells fuse with liver cells to form hybrids that drive hepatocyte proliferation, essential for restoring liver mass.
Area of Science:
- Hepatology
- Stem Cell Biology
- Regenerative Medicine
Background:
- The liver's capacity for regeneration after partial removal (hepatectomy) is well-established in humans and rodents.
- Hepatocyte proliferation and cell cycle re-entry are considered the primary drivers of liver mass restoration.
- Bone marrow cells (BMCs) are known to infiltrate the liver following surgical resection.
Purpose of the Study:
- To investigate the role of bone marrow cell recruitment in liver regeneration after hepatectomy.
- To elucidate the mechanism by which bone marrow cells contribute to liver regeneration.
- To determine the necessity of bone marrow-derived hybrids for efficient liver regeneration.
Main Methods:
- Surgical hepatectomy in rodent models.
- Experimental blockade of bone marrow cell recruitment to the liver.
- Genetic manipulation to ablate bone marrow-derived hybrids.
- Cell fusion analysis and proliferation assays.
- Mathematical modeling of regeneration dynamics.
Main Results:
- Blocking bone marrow cell recruitment significantly impairs liver regeneration post-hepatectomy.
- Mobilized hematopoietic stem and progenitor cells (HSPCs) from bone marrow fuse with hepatocytes, forming hybrid cells.
- These bone marrow-derived hybrids proliferate earlier than hepatocytes.
- Genetic elimination of these hybrids severely hinders hepatocyte proliferation and overall liver regeneration.
- Mathematical models confirm the critical role of bone marrow-derived hybrids in driving regenerative proliferation.
Conclusions:
- Bone marrow-derived hybrids are essential for initiating and driving efficient liver regeneration after hepatectomy.
- The fusion of hematopoietic stem and progenitor cells with hepatocytes represents a novel mechanism in liver repair.
- Targeting bone marrow cell mobilization or hybrid formation could offer therapeutic strategies for liver regeneration.
