Invitro Hepatic like Differentiation of Umbilical Cord-Derived Mesenchymal Stem Cells through FGF and IGF Factor Preconditioning.

Introduction: Liver diseases remain a major global health burden, with limited treatment options for advanced hepatic dysfunction.Current treatment options are limited and mainly supportive, with liver transplantation being the only definitive therapy in advanced cases.Stem cell-based therapies have emerged as a promising alternative due to their regenerative and immunomodulatory properties.Stem cells can differentiate and produce identical daughter cells.Umbilical cord-derived mesenchymal stem cells (UC-MSCs) hold promise for liver regeneration but show limited hepatic differentiation efficiency.Preconditioning with FGF and IGF may enhance their differentiation, survival, and functional potential.This study aims to investigate the effect of FGF and IGF pre-treatment on the differentiation capacity of UC-MSCs and their potential application in regenerative therapy for liver fibrosis or cirrhosis.Methods: Cell viability was evaluated through MTT, crystal violet, and trypan blue assays.For the assessment of differentiation potential, ELISA and Immunocytochemistry of HNF4α and ASGPR1 were performed, for angiogenesis and apoptosis, ELISA of VEGF and p53 were performed.Furthermore, antioxidant enzyme activity was also assessed.Results: UC-MSCs preconditioned with FGF and IGF exhibited significantly enhanced viability and reduced cell death, as confirmed by MTT, crystal violet, trypan blue assays, and ELISA of VEGF and P53.ELISA and immunocytochemistry of HNF4α and ASGPR1 demonstrated marked upregulation of these hepatic markers in the preconditioned groups.The gene expression analysis confirmed superior regenerative potential in the FGF+IGF-treated group.Antioxidative analysis further validated a higher level of antioxidative potential in preconditioned cells.Conclusion: Preconditioned UC-MSCs offer a promising cellbased alternative to liver transplantation by enhancing regeneration, reducing apoptosis, promoting angiogenesis and increasing antioxidant defense in damaged liver tissue.Wilson's disease and urea cycle disorders result from enzyme deficiencies that cannot be corrected through medication alone.Similarly, end-stage liver cirrhosis caused by chronic hepatitis or autoimmune hepatitis leads to extensive fibrosis and hepatocyte depletion, where liver transplantation remains the only standard option.However, due to donor organ shortages and post-transplant complications, stem cell-derived hepatocyte-like cells offer a viable and scalable alternative.These cells can repopulate the damaged liver, restore lost functions, and potentially correct genetic enzyme defects through cell-based gene therapy [4] .The present study introduces an innovative intraoperative and intramedullary delivery of laser therapy using long sterile optical fibers, allowing direct irradiation at the fracture site.This method differs from prior studies in which PBMT was administered transcutaneously, often resulting in limited penetration and variable dosimetry.By applying PBMT directly within the medullary canal during surgery, this technique may enhance energy delivery to the osteogenic niche and bone marrow environment, potentially influencing resident mesenchymal stem cells and improving