Giannoukakis N, Pietropaolo M, Trucco M
Dept of Pathology, and Diabetes Institute, University of Pittsburgh School of Medicine, Rangos Research Center, PA 15213, USA.
Diabetes Nutr Metab. 2002 Jun;15(3):173-203.
Although diabetes mellitus is a manageable disorder, the associated complications that result in significant morbidity and mortality worldwide necessitate novel approaches of pharmacologic, cell, and gene therapy for an eventual cure. A significant number of animal studies have demonstrated the potential of restoring normoglycemia by islet transplantation in the context of immunoregulation achieved by gene transfer of immunoregulatory genes to allo- and xenogeneic islets ex vivo. Examples include viral vector-mediated gene transfer of immunosuppressive cytokines, proteins that block co-stimulation and molecules that prevent apoptotic cell death. Additionally, gene and cell therapy has also been used to induce tolerance to auto- and alloantigens and to generate the tolerant state in autoimmune rodent animal models of Type 1 diabetes mellitus (T1DM) or rodent recipients of allogeneic/xenogeneic islet transplants. Gene transfer of putative autoantigens is one example. The achievements of gene and cell therapy in Type 2 diabetes mellitus (T2DM) are less evident, but seminal studies promise that this modality can be relevant to treat and perhaps prevent the underlying causes of the disease including obesity and insulin resistance. Herein, we present an overview of the current status of drug, gene and cell therapy for T1DM and T2DM and we propose novel therapeutic options that could be clinically useful.
尽管糖尿病是一种可控制的疾病，但在全球范围内，其相关并发症会导致严重的发病率和死亡率，因此需要采用新的药物、细胞和基因治疗方法来实现最终治愈。大量动物研究表明，通过体外将免疫调节基因转移到同种异体和异种胰岛来实现免疫调节的情况下，胰岛移植有可能恢复正常血糖水平。例如，病毒载体介导的免疫抑制细胞因子基因转移、阻断共刺激的蛋白质以及防止细胞凋亡的分子。此外，基因和细胞疗法也已用于诱导对自身抗原和同种异体抗原的耐受性，并在1型糖尿病（T1DM）的自身免疫性啮齿动物模型或同种异体/异种胰岛移植的啮齿动物受体中产生耐受状态。推定自身抗原的基因转移就是一个例子。基因和细胞疗法在2型糖尿病（T2DM）中的成果不太明显，但开创性研究表明，这种治疗方式可能与治疗甚至预防包括肥胖和胰岛素抵抗在内的疾病潜在病因相关。在此，我们概述了T1DM和T2DM的药物、基因和细胞治疗现状，并提出了可能具有临床应用价值的新治疗方案。
