Brevini T A L, Pennarossa G, Acocella F, Brizzola S, Zenobi A, Gandolfi F
Department of Health, Animal Science and Food Safety, Università Degli Studi Di Milano, Via Celoria 10, 20133 Milano, Italy.
Department of Health, Animal Science and Food Safety, Università Degli Studi Di Milano, Via Celoria 10, 20133 Milano, Italy.
Vet J. 2016 May;211:52-6. doi: 10.1016/j.tvjl.2016.02.014. Epub 2016 Mar 4.
Diabetes is among the most frequently diagnosed endocrine disorder in dogs and its prevalence continues to increase. Medical management of this pathology is lifelong and challenging because of the numerous serious complications. A therapy based on the use of autologous viable insulin-producing cells to replace the lost β cell mass would be very advantageous. A protocol to enable the epigenetic conversion of canine dermal fibroblasts, obtained from a skin biopsy, into insulin-producing cells (EpiCC) is described in the present manuscript. Cells were briefly exposed to the DNA methyltransferase inhibitor 5-azacytidine (5-aza-CR) in order to increase their plasticity. This was followed by a three-step differentiation protocol that directed the cells towards the pancreatic lineage. After 36 days, 38 ± 6.1% of the treated fibroblasts were converted into EpiCC that expressed insulin mRNA and protein. Furthermore, EpiCC were able to release insulin into the medium in response to an increased glucose concentration. This is the first evidence that generating a renewable autologous, functional source of insulin-secreting cells is possible in the dog. This procedure represents a novel and promising potential therapy for diabetes in dogs.
糖尿病是犬类中最常被诊断出的内分泌疾病之一，其患病率持续上升。由于存在众多严重并发症，这种病症的药物治疗是终身的且具有挑战性。基于使用自体有活力的胰岛素产生细胞来替代丢失的β细胞团的疗法将非常有利。本手稿描述了一种方案，可使从皮肤活检获得的犬真皮成纤维细胞发生表观遗传转化，成为胰岛素产生细胞（EpiCC）。细胞短暂暴露于DNA甲基转移酶抑制剂5-氮杂胞苷（5-aza-CR）以增加其可塑性。随后是一个三步分化方案，引导细胞向胰腺谱系分化。36天后，38±6.1%的经处理的成纤维细胞转化为表达胰岛素mRNA和蛋白质的EpiCC。此外，EpiCC能够响应葡萄糖浓度升高而将胰岛素释放到培养基中。这是首次有证据表明在犬类中生成可再生的自体功能性胰岛素分泌细胞来源是可能的。该程序代表了一种用于犬类糖尿病的新颖且有前景的潜在疗法。
