Rejuvenating bone marrow hematopoietic reserve prevents regeneration failure and hepatic decompensation in animal model of cirrhosis

• DOI: 10.3389/fimmu.2024.1439510
• Publication Date: 2024-08-12T09:17:16Z
• Authors: Nidhi Nautiyal; Deepanshu Maheshwari; Dhananjay Kumar; E. Pranshu Rao; Dinesh Mani Tripathi; Sandeep Kumar; Sunidhi Diwakar; Manisha Bhardwaj; Sujata Mohanty; Prakash Baligar; Anupama Kumari; Chhagan Bihari; Subhrajit Biswas; S. K. Sarin; Anupam Kumar
• Keywords: Decompensation; Liver Regeneration; Bone marrow failure

Background and aim Bone marrow stem cells (BM-SCs) their progeny play a central role in tissue repair regeneration. In patients with chronic liver failure, bone (BM) reserve is severally compromised they showed marked defects the resolution of injury infection, leading to failure onset decompensation. Whether BM cause or consequence during cirrhosis not known. this study, we aimed determine underlying relationship between regeneration cirrhosis. Methodology C57Bl/6(J) mice were used develop through intra-peritoneal administration carbon tetrachloride (CCl4) for 15 weeks (0.1-0.5 ml/kg). Animals sacrificed study transition defects. To restore BM-SC reserve; healthy infused via intra-BM infusion assessed changes injury, regeneration, reserve. Results Using CCl4-induced animal - model cirrhosis, loss BM-SCs occurred before non-acute Intra-BM induced repopulation native hematopoietic (HSCs) cirrhotic BM. Restoring BM-HSCs augments macrophage-mediated clearance infection inflammation dampens neutrophil-mediated inflammation, accelerates fibrosis regression, enhances hepatocyte proliferation, delays Conclusion These findings suggest that underlies innate immune function liver, drives We further provide proof-of-concept rejuvenating BM-HSC can serve as potential therapeutic approach preventing decompensated