Reduced Mobilisation of Hematopoietic Stem Cells After Hepatic Resection for Malignant Liver Disease

Abstract

Recent studies have demonstrated that hematopoietic stem cells (HSCs) can mobilize following liver resection, thus contributing to the repair of hepatic damage. Aim of this study has been to determine whether the nature of the hepatic lesion (benign vs. malignant disease) can give rise to a different degree of mobilisation of HSCs. Two groups of patients were selected: the first included seven patients undergoing hepatic resection (five major and two minor) for a benign liver disease (focal nodular hyperplasia, hemangioma cavernosa, angioma, biliary adenofibroma) and the second included seven patients undergoing hepatic resection (five major and two minor) for a malignant (either primary or secondary) liver disease. White blood cell count and CD34+ (percentage and total number) at time T(0) (basal value before surgery) and at time T(1) (value on the sixth-eighth day after surgery) have been evaluated by standard methods. In the group undergoing hepatic resection for a benign liver disease, a significant increase of CD34+ cells, both in percentage (0.082 +/- 0.043 vs. 0.048 +/- 0,026, p = 0.041) and in absolute number (8.14 +/- 5.95 vs. 3.26 +/- 2.63, p = 0.018) have been documented, as opposed to the group of patients affected with a malignant liver disease, where no significant variation has been observed (CD34+ %: 0.044 +/- 0.033 vs. 0.041 +/- 0.031, p: n.s.; CD34+ total number: 3.52 +/- 2.56 vs. 2.27 +/- 2.01, p = n.s.) These results show a different bone marrow response to the surgical liver resection depending on the nature of the lesion, thus emphasizing a reduced mobilisation of HSCs in the malignant diseases. Since it has been documented that the type of the hepatic lesion can induce a different regenerative response, it has to be explained how the neoplastic lesions can negatively influence the mobilization of HSCs. It can be hypothesized that a variety of humoral factors, including stromal cell-derived factor, matrix metalloproteinases, hepatocyte growth factor and interleukin-8 can influence the process of mobilization of HSCs after liver resection surgery. These substances are also involved in the mechanisms of development and metastasising of many tumours. It is probably in this context that a reason may be found for the different mobilisation of hematopoietic stem cells, depending on the nature of the hepatic lesion treated, that was encountered in this study.

Differential Bone Marrow Hematopoietic Stem Cells Mobilization in Hepatectomized Patients

“…22 Menegazzo et al have shown that the type of the hepatic lesion influences the regenerative response after hepatic resection, with a reduced mobilization of HSC in the malignant liver diseases. 21 In the present study, the analysis of a comparatively higher number of patients has shown no association between the levels of CD34 + cells and the clinical characteristic of the patients. However, it is interesting to note that the patients with hepatocellular carcinoma and metastasis showed lower percentages of BMSC mobilization (14% and 40%, respectively) compared to other type of pathologies.…”

Hematopoietic stem cell mobilization into the peripheral circulation in patients with chronic liver diseases

“…This hypothesis was adopted by an important study reporting the reduced mobilization of BMHSC in malignancy after hepatic resection. This effect was found to be caused by the downregulation of some factors including stromal cell‐derived factor (SDF), matrix metalloproteinases, hepatocyte growth factor and interleukin‐8 …”

“…This effect was found to be caused by the downregulation of some factors including stromal cell-derived factor (SDF), matrix metalloproteinases, hepatocyte growth factor and interleukin-8. 27 Lack of BMHSC mobilization to the circulation was then confirmed by the failure of such cells to engraft in the hepatic tissue. No difference in the frequency of CD133 + stem cells was found in injured liver tissue with variable degrees of severity, denoting that neither residing nor BMHSC were activated.…”

“…PB hematopoietic stem cell levels have been found to be elevated after excessive liver resection in healthy liver donors as well as after partial orthotopic liver transplantation showing serious liver graft injury and increased immune response. However, other studies have shown no evidence of BMHSC mobilization during acute decompensation of cirrhotic liver or after a hepatectomy in patients with malignant liver disease.…”

Serum levels of HGF, IL-6, and TGF-α after benign liver tumor resection

“…After resection of FNH and hemangioma tumors, the serum levels of HGF, IL-6, and TGF-a increased at similar rates during the first 24 h, followed by significant declines back to pre-operative levels. cell (HSC) mobilization after liver resection of a malignant disease [31]. Additionally, HSC's were shown to play a role in the production of humoral factors which indirectly support hepatic recovery and may induce an alternate regenerative response depending on the nature of the lesion [32].…”