Human fetal liver derived stem cell transplantation as supportive modality in the management of end stage decompensated liver cirrhosis

Abstract

Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a few people. With a tremendous upsurge in the mortality rate of patients with liver disorders worldwide, there is a need to search for an alternative therapeutic tool that can combat the above limitations and serve as a supportive therapy in the management of liver diseases. Cell therapy using human fetal liver-derived stem cells can provide great potential to conservatively manage end-stage liver diseases. Therefore, the present investigation aimed to study and prove the safety and efficacy of human fetal liver-derived stem cell transplantation in patients with end-stage liver cirrhosis. Twenty-five patients with liver cirrhosis of different etiologies were infused with human fetal liver-derived stem cells (EpCAM+ve) labeled with Tc-HMPAO through hepatic artery. Our high throughput analysis using flow cytometry, RT-PCR, and cellular characterization exemplifies fetal liver cells with their high proliferation rate could be the best source for rejuvenating the diseased liver. Further, no episodes related to hepatic encephalopathy recurred in any of the subjects following hepatic stem cell transplantation. There was marked clinical improvement observed in terms of all clinical and biochemical parameters. Further, there was decrease in mean MELD score (p < 0.01) observed in 6 months follow-up in all patients. Therapy using human fetal liver stem/progenitor cells offers a potentially supportive modality to organ transplantation in the management of liver diseases.

Hepatic Progenitors of the Liver and Extra-Hepatic Tissues

“…This is especially the case for hepatic progenitors isolated from human livers. Hepatic progenitors represent a population with potential advantages over total liver cell suspensions or hepatocytes for cell transplantation in patients (29,128), for review see (129). Because of their high proliferation and differentiation potential a major advantage for transplantation of stem cells over total liver cell suspensions would be the requirement for less cell numbers to inject, which would decrease the risks associated with transplanting high cell numbers.…”

Stem Cells: General Features and Characteristics

“…Rat Dlk cells isolated from mid-gestational fetal liver exhibit characteristics expected for hepatic stem/progenitor cells. Thus, fetal liver cells may be suitable for overcoming the limitations in engraftment and to allow a functional correction of the disease phenotype (Khan, et al, 2010), as well as in use of artificial liver devices. Hematopoietic cells are fetal stem cells in the umbilical cord after the birth of a baby.…”

“…A single cell in the c-Met + CD49f -low c-Kit -CD45 -Ter119 -fraction from mid-gestational fetal liver revealed the capacity of self-renewal in vitro and bipotential differentiation, indicating the containing of hepatic stem cells in this defined fraction, while the hepatic progenitor cells lack the capacity of self-renewal. As an in vitro cultivation protocol of fetal hepatic stem cells has been established, the fetal liver cells may be promised for the hepatic cell amount in engraftment and the functional correction of the disease phenotype (Khan, et al, 2010), which should be better over the artificial liver devices. Extra hepatic stem cells have been demonstrated to be involved in liver regeneration too in mice and rats studies (Herzog, et al, 2003).…”

Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions

“…Hepatic artery: Hepatic artery can be accessed through trans femoral, trans radial, trans brachial. In our experience hepatic artery route is more convenient compared to hepatic portal vein [91]. Though highly efficient, direct deliveries into liver might pose the risk of occlusion and in certain cases fibrosis, due to portal hypertension and embolism of cells.…”

“…For example, our group demonstrated the efficacy of fetal hepatic progenitor cells, delivered through the hepatic artery in 25 cases of de-compensated liver cirrhosis, resulting in significant clinical improvement in more than 80 % cases. The hepatic angiogram showed no sign of thrombosis/narrowing/ischemia in the hepatic artery when analyzed after successive time intervals (Figure 3) [91].…”