Transplantation Research Center, Division of Nephrology, Children's Hospital/Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
Endocr Rev. 2011 Dec;32(6):725-54. doi: 10.1210/er.2011-0008. Epub 2011 Aug 23.
Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs.
目前旨在治愈 1 型糖尿病（T1D）的方法使极少数患者能够不依赖胰岛素。在这篇综述中，我们重新审视了基于干细胞（SC）的应用在治愈 T1D 中的作用。T1D 的最佳治疗方法应该理想地保留剩余的β细胞，恢复β细胞功能，并保护替代的胰岛素产生细胞免受自身免疫。SCs 具有免疫和再生特性，可以利用这些特性来改善 T1D 的治疗效果；事实上，SCs 可以通过重塑免疫反应和抑制自身反应性 T 细胞功能来重新建立对β细胞的外周耐受性。此外，SC 衍生的胰岛素产生细胞能够在小鼠中植入并逆转高血糖。骨髓间充质干细胞表现出低免疫原性表型和广泛的免疫调节能力，它们已被证明可以治愈新发生的糖尿病非肥胖型糖尿病（NOD）小鼠，并且目前正在两项临床试验中进行评估。脐带血干细胞已被证明可以促进调节性 T 细胞的生成，从而使 NOD 小鼠的高血糖得到逆转。接受脐带血干细胞治疗的 T1D 患者在没有对糖代谢控制产生重大影响的情况下也没有出现任何不良反应。尽管造血干细胞很少使 NOD 小鼠的高血糖逆转，但它们在人类中具有显著的免疫调节特性；新发生高血糖的 T1D 患者已成功通过自体非清髓性造血干细胞移植恢复正常血糖水平。最后，胚胎干细胞也提供了令人兴奋的前景，因为它们能够产生对葡萄糖有反应的胰岛素产生细胞。应该主要通过减轻对干细胞潜在致癌性的担忧来缓解过度热情。
