Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy.
Maria Cecilia Hospital, GVM Care & Research, E.S: Health Science Foundation, Via Madonna di Genova 1, 48033 Cotignola, Italy.
Int J Mol Sci. 2018 Dec 15;19(12):4064. doi: 10.3390/ijms19124064.
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.
目前,肝脏疾病最有效的治疗方法是肝移植,但由于器官供体短缺、经济原因以及需要终身免疫抑制等因素,其应用受到限制。间充质干细胞(MSC)移植为人类和兽医医学中治疗肝脏疾病提供了一种很有前途的替代方法。有趣的是,这些疾病在人类和犬种中表现出共同的临床和病理特征;因此,犬可能是人类临床研究的自发模型。本研究旨在对犬脂肪来源间充质干细胞(cADSCs)进行鉴定,并将其与人类间充质干细胞(hADSCs)进行比较,以支持犬模型在肝脏疾病的细胞治疗中的应用。cADSCs 和 hADSCs 均从脂肪组织样本中成功分离。两种细胞群均具有相似的成纤维细胞样形态、干细胞表面标志物表达和增殖率。在检查多能分化能力时,cADSCs 的成脂能力较低,成骨分化能力较高。两种细胞群在控制温度的 PBS 中保存长达 72 小时,仍保持高活力,表明具有短期储存和运输的可能性。此外,我们评估了自体 ADSCs 移植在犬肝脏疾病中的疗效。所有动物的肝功能均显著改善,这表现在细胞移植后测量的肝生物标志物水平降低和细胞学标本评估上。这些有益的效果似乎与干细胞的免疫调节特性有关。因此,我们认为这种方法可能是未来将结果转化为人类临床实践的起点。