P005

Bone marrow-derived stem cells in human liver diseases

Estela Solanas¹, F. Javier Arangurena², Javier Godino¹, Jose Antonio Moreno³, M. Angel De Gregorio⁴, Joaquin Medrano⁴, Jose Carlos Segovia⁵, Sara Lorente², Trinidad Serrano²

¹Instituto Aragones de Ciencias de la Salud, IIS Aragon, Zaragoza; ²Hepatology and Liver Transplantation, Hospital Clinico Lozano Blesa, Zaragoza; ³Hematology, Hospital Clinico Lozano Blesa, Zaragoza; ⁴Interventional Radiology, Hospital Clinico Lozano Blesa, Zaragoza; ⁵Hematopoiesis and Gene Therapy, CIEMAT, Madrid, Spain

Bone marrow (BM) seems to play an important role in regeneration after liver injury. Several growth factors and cytokines such as HGF, SDF-1 and VEGF, released during injury act as powerful chemoattractantsto BM progenitor cells. One of the primary signals that the stemcells receive after tissue injury may be the hypoxia-inducedlocal activation of HGF that could act, in a gradient-dependent manner, to induce stem cell migration into thedamaged tissue. Although there are data supporting this hypothesis in animal studies, there is little information about these phenomena in humans.

Objective: To study the role and mechanisms of BM progenitor cells in liver injury in humans.

Patients and methods: Peripheral blood was recollected from 16 patients with acute hepatitis (AH), 7 with liver cirrhosis (LC), 7 with acute on chronic liver disease (AOC) and 7 healthy controls (HC). BM stem cells were analyzed by flow cytometry measuring CD34+, CD131+, CXCR4+, VEGF-2R+, c-KIT+, populations. Growth factors and cytokines (VEGF, HGF, SDF-1, G-CSF, SCF, MPP9, IL-3, IL-6 and IL-8) were quantified by luminex technology in peripheral and suprahepatic blood.

Results: Significant BM mobilization was detected in patients with HA. In this group CD34+ cells were 0.052%±0.03 versus 0.020%±0.01 in LC patients, and VEGFR-2+ cells were 0.078%±0.08 versus 0.017± 0.09. AH group had also higher levels of VEGF (933.4±824.7 pg/ml versus 464±730 pg/ml) and HGF (6700.9±4561 pg/ml versus 1930.6±886 pg/ml) than LC patients. All these differences were significant (p<0,05). HGF levels were three times higher in suprahepatic (24879±31119 pg/ml) than in peripheral blood (8038±8613 pg/ml).

Conclusion: Growth factors released in acute liver injury could induce bone marrow mobilization indicatingthat bone marrow stem cell could play an important role in liver regeneration in humans.