Adipose-derived stem cell-based treatment for acute liver failure

Abstract

IntroductionAcute liver failure (ALF) is a highly lethal disease, for which effective therapeutic methods are limited. Although allogeneic liver transplantation is a viable treatment method for ALF, there is a serious shortage of liver donors. Recent studies suggest that stem cell transplantation is a more promising alternative. Hence, we investigate whether human adipose-derived stem cells (ASCs) have the therapeutic potential for ALF in this study based on the studies of rat models.MethodsSprague Dawley rats were used to establish ALF models by D-galactosamine injection. These rats were randomly divided into a human ASC-treated group and a phosphate-buffered saline (PBS) control group. The human ASCs or PBS was transplanted through the spleen of rats. The indices of hepatic function and hepatic histology were dynamically detected, and the survival rates of rats were also counted. Double-fluorescence immunohistochemistry was employed to detect the ASC fate after transplantation. Moreover, both concentrated ASC conditional media and ASC lysates were transplanted through the femoral vain of rats to investigate the therapeutic potential for ALF.ResultsThe ASC transplantation group showed improved viability in comparison with the sham control. Histological and biochemical analysis suggested that liver morphology and function were improved in terms of cell proliferation and apoptosis. Although a plethora of ASCs persist in the spleen, the improvement in liver function was obvious. However, ASCs did not differentiate into hepatocytes after engrafting to livers within 3 days. In addition, both concentrated serum-free ASC conditional media and ASC lysates, characterized by high levels of hepatocyte growth factor and vascular endothelial growth factor, demonstrated obvious improvement in terms of high survival rates of ALF rats.ConclusionOur data suggest that ASC transplantation has the potential for ALF treatment partly by the mechanism of secreting growth factors contributing to liver regeneration.

Beneficial effect of corticosteroids for patients with severe drug‐induced liver injury

“…Nevertheless, organ shortages, disease progression and high medical cost limit the application of liver transplantation. Given this background, developing therapies other than transplantation has been greeted with growing enthusiasm . Consequently, as a result of its idiosyncratic and immune‐based pathogenesis, corticosteroids have been introduced to treat DILI, especially in severe cases who are more likely to develop ALF.…”

“…Given this background, developing therapies other than transplantation has been greeted with growing enthusiasm. 23 Consequently, as a result of its idiosyncratic and immune-based pathogenesis, corticosteroids have been introduced to treat DILI, 24 especially in severe cases who are more likely to develop ALF. However, the efficacy of corticosteroids for DILI has still not been clearly elucidated to date and it is not routinely recommended for DILI.…”

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

“…Some studies proved that MSCs could differentiate into hepatocyte-like cells (HLCs) in vivo, considered as one of the mechanisms of MSCs in the treatment of liver failure [26,27]. While some experiments have suggested that MSCs cannot differentiate into HLCs after engrafting even if the improved survival, reduced alanine aminotransferase (ALT) and relieved liver injury [28]. These ndings demonstrate that the effective performance of MSCs in the treatment of liver failure is not just dependent on the supplementing exogenous hepatocytes.…”

Comparative Light and Electron Microscopic Study on the Therapeutic Efficacy of Adipose Derived Stem Cells Versus Exosomes for Experimentally Induced Acute Corneal Injuries in Rats

“…They include a type of multipotent adult stem cells isolated from adipose tissue and have the capacities of self-regeneration and differentiation into various cell lineages [9,10]. Both BMSCs and ADSCs have common biological properties such as cell surface markers, gene expression profile, immunosuppressive features, and differentiation capacity, but ADSCs have more proliferative capacity than that of BMSCs [11]. ADSCs have been used in a recent technique for wound repair, regeneration, and tissue engineering procedures because the adipose tissue is easy to gain and process; in addition, the isolated cells expand rapidly and differentiate into different cell types in vitro [12][13][14].…”