Article
Correlation of peripheral CD133+/CD45+ cells with the extend of liver regeneration and the stemness marker alpha feto protein after hepatic resection – role of HGF and CXCL12 for stem cell mobilisation
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Published: | May 20, 2011 |
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Introduction: We previously demonstrated peripheral mobilisation of CD133+/CD45+ hematopoietic stem cells after extended forms of clinical hepatectomy. In this study we correlated peripheral CD133+/CD45+ cell mobilisation with the extend of resected liver volume and its regain, with paracrine factors like hepatic growth factor (HGF), CXCL12 (SDF-1) and alpha feto protein (AFP).
Materials and methods: Peripheral progenitor mobilisation was investigated by FACS-analyses in 30 hepatectomy patients. Exact extend of liver volume loss and regain by day-21 after hepatic resection was determined by CTscan volumetry. 20 patients with resection volume of less than 20% (groupA;n=20) were contrasted to 10 patients with a resection extend of 30-67% (groupB;n=10). Mobilising capacity of HGF and SDF-1 for CD133+/CD45+ BMSCs was investigated in two migration assays (UnderAgarose ChemotaxisAssay, BoydenChamber TranswellAssay).
Results: In groupB we observed increased levels of HGF, SDF-1 in the first 6h and of AFP beyond 24h if compared to groupA. Beyond an augmented mobilisation of CD133+/CD45+ cells from day-2 on in the large resection group, levels of early CD133+/CD45+ stemcell mobilisation correlated directly with the level of hepatic volume regain by day-21. The mobilisation of CD133+/CD45+ cells on day-4 after liver resection in group B was directly correlated with the levels of AFP serum levels on day-6 after hepatectomy. In in-vitro migration assays human bone marrow (BM) derived CD133+ cells isolated by MACS showed a specific target-directed migration towards recombinant HGF and SDF-1 gradients in concentration-dependant manners.
Conclusion: These data suggest HGF and SDF-1 to play a role for mobilisation of CD133+ stem cells from BM in the scenario of liver regeneration subsequent to hepatic resection. Whether peripheral mobilisation of CD133+ BM stem cells that correlates with levels of liver regeneration after hepatectomy results in integration of those cells to intra-hepatic stem cell comparments, as possibly suggested here by AFP expression data, needs to be further explored.