Therapeutic Potential of Autologous Adipose-Derived Stem Cells for the Treatment of Liver Disease

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.

Hyperbaric Oxygen Therapy Improves the Osteogenic and Vasculogenic Properties of Mesenchymal Stem Cells in the Presence of Inflammation In Vitro

“…Analyzed osteogenic markers included runt related transcription factor 2 (RUNX2), osterix (OSX), alkaline phosphatase, liver/bone/kidney (ALP), osteocalcin (OCN), osteopontin (OPN), and tumor necrosis factor (ligand) superfamily, member 11 (RANKL); gene expression of vascular endothelial growth factor A (VEGFA) and kinase insert domain receptor (KDR) was additionally evaluated ( Figure 6). TFRC was chosen as reference gene for real-time PCR data normalization since its expression resulted stable during MSCs osteogenic differentiation, as also established in our previous works [23,24]. The levels of gene expression for the key transcription factor RUNX2 slightly increased with culture time both in the treated and control groups, without significant differences between the various conditions ( Figure 6A).…”

“…To the best of our knowledge, the direct effects of the HBO therapy on metabolic activity and osteogenic differentiation of hADSCs grown in a simulated pro-inflammatory environment have not been investigated previously. In this study, hADSCs isolated from human adipose tissue samples, then cultured and differentiated following the same protocol published in a recent work from our laboratory, were used [23]. In that work, flow cytometric immunophenotypic characterization showed that >99% of cells were positive for the MSCs-specific markers CD44, CD73, CD90, and CD105, and simultaneously negative for the hematopoietic markers CD14, CD34, and CD45.…”

Scintigraphic Tracking of 99mTechnetium Labelled Equine Peripheral Blood-Derived Mesenchymal Stem Cells After Intravenous, Intramuscular and Subcutaneous Injection in Healthy Dogs.

“…CB, ED, GP, LT and JHS 1,2 are all employed by GST. JHS is an inventor of a pending patent covering the described immunomodulating technology owned by GST (EP19162270.3).…”

“…JHS is an inventor of a pending patent covering the described immunomodulating technology owned by GST (EP19162270.3). EDP, CB and JHS 1,2 are the inventors of a patent covering the 99m Tc labelling of ePB-MSCs owned by GST (EP19200152.7). The content of this manuscript contains a stem cell product under development owned by GST.…”

“…Over the past decade the use of mesenchymal stem cell (MSC) treatments in dogs has been investigated as an interesting and innovative alternative to current conventional therapies. Promising results were described for a variety of conditions such as osteoarthritis, tendon and ligament lesions, liver diseases, atopic dermatitis and in ammatory bowel disease [1,2,3,4,5,6,7,8]. The most frequently used sources of canine MSCs are autologous or allogeneic adipose tissue derived MSCs.…”