Abstract
Currently, the most effective therapy for liver diseases is liver transplantation, but its use is limited by organ donor shortage, economic reasons, and the requirement for lifelong immunosuppression. Mesenchymal stem cell (MSC) transplantation represents a promising alternative for treating liver pathologies in both human and veterinary medicine. Interestingly, these pathologies appear with a common clinical and pathological profile in the human and canine species; as a consequence, dogs may be a spontaneous model for clinical investigations in humans. The aim of this work was to characterize canine adipose-derived MSCs (cADSCs) and compare them to their human counterpart (hADSCs) in order to support the application of the canine model in cell-based therapy of liver diseases. Both cADSCs and hADSCs were successfully isolated from adipose tissue samples. The two cell populations shared a common fibroblast-like morphology, expression of stemness surface markers, and proliferation rate. When examining multilineage differentiation abilities, cADSCs showed lower adipogenic potential and higher osteogenic differentiation than human cells. Both cell populations retained high viability when kept in PBS at controlled temperature and up to 72 h, indicating the possibility of short-term storage and transportation. In addition, we evaluated the efficacy of autologous ADSCs transplantation in dogs with liver diseases. All animals exhibited significantly improved liver function, as evidenced by lower liver biomarkers levels measured after cells transplantation and evaluation of cytological specimens. These beneficial effects seem to be related to the immunomodulatory properties of stem cells. We therefore believe that such an approach could be a starting point for translating the results to the human clinical practice in future.
Highlights
Liver diseases are a widespread problem for national health care systems over the world
Human adipose-derived stem cells formed several colonies, which disappeared with subsequent passages; these colonies were not present in the canine cell population at passage 1 (p1)
Immunostaining of the actin cytoskeleton with phalloidin better revealed the morphology of canine adipose-derived stem cells (ADSCs) and human adipose-derived stem cells (hADSCs) (Figure 1B,D)
Summary
Liver diseases are a widespread problem for national health care systems over the world. The development of alternative methods for treatment of liver disease is highly requested. In this context, the emerging field of regenerative medicine offers new approaches based on cell transplantation or organ engineering. Organ engineering has the potential to solve the problem of liver donor shortage, cell transplantation is a much less invasive and expensive approach. This consists in the transfusion or injection of cells aimed at increasing the regeneration capacity in recipient liver and improving the restoration of its structure and function [2]. The main limitation remains the scarcity of donor livers from which high-quality primary hepatocytes can be isolated [4]
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