Islet cell biology, regeneration, and transplantation.
Islet cell biology, regeneration, and transplantation.
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DOI：
10.1155/2012/139787
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发表时间：
2012
影响因子：
2.8
通讯作者：
Naziruddin B
中科院分区：
文献类型：
--
作者：
Balamurugan AN;Kumaravel V;Pugazhenthi S;Naziruddin B
以胰岛的生物学、再生和移植为中心的研究继续对不同形式糖尿病的发展提供了重要的理解，并为寻求“治愈”提供了进一步的动力。糖尿病是产生胰岛素的胰腺β细胞数量不足的一种表现。1型的特点是由于自身免疫攻击导致β细胞完全丧失，而2型的特点是由于胰岛素抵抗代偿减少导致β细胞相对缺乏[1,2]。恢复β细胞质量和逆转糖尿病可以通过两种方法来实现：通过β细胞的内源性再生或从外源性来源移植β细胞；最近科学技术的进步促进了这两方面的进步。在第一种方法中，虽然在体外扩增成熟β细胞的努力取得了有限的成功，但从胚胎和成体干细胞或胰腺祖细胞中再生β细胞已显示出前景。了解β细胞特异性转录因子在β细胞表型转分化中的作用对进一步研究至关重要。使用生长因子、激素和小分子的药理学方法也被证明可以促进β细胞的增殖和功能。在第二种方法中，从尸体供体胰腺中分离胰岛移植已被证明是替代1型糖尿病患者耗尽β细胞的一种直接有效的方法，使其能够独立于外源性胰岛素治疗[3,4]。然而，为了保存移植的β细胞群，胰岛移植受者需要免疫抑制，而在目前的治疗方案下，免疫抑制是已知的β细胞毒性。这一限制最终导致移植胰岛的长期功能不佳，并使致力于为患者提供持久治疗的医学界感到沮丧。在这一期特刊中，介绍了在不同研究领域取得的重大进展，旨在克服目前胰岛再生和移植的局限性。在这种公开提交格式收到的众多论文中，经过同行评审后，已推荐发表选定的论文。这一特别版介绍了一系列令人兴奋的论文，这些论文描述了提高β细胞和胰岛移植可用性的策略，以及提高它们移植后的存活率。很明显，挑战胰岛移植进一步成功的主要障碍之一是缺乏合适的供体胰腺。同种异体胰岛移植的长期存活率较差使这一问题更加复杂。这篇评论文章由f.c。Chou等人总结了许多调节移植胰岛免疫反应的策略。基因治疗为设计胰岛移植物抵抗炎症诱导的细胞凋亡和产生免疫抑制分子来减弱t细胞反应提供了有力的工具。此外，还讨论了利用ipsc衍生的胰腺β样细胞开发患者特异性的自体β细胞替代疗法的潜力。本文提出的该领域的关键问题包括(i)目标基因在胰岛中的持续时间和表达水平，（ii）使用病毒载体进行可能导致插入突变和宿主免疫原性的直接基因治疗，
Research studies centered on the biology, regeneration, and transplantation of islets continue to shed significant understanding on the development of different forms of diabetes and provide further impetus for the quest to find a “cure.” Diabetes is a manifestation of an inadequate mass of insulinproducing pancreatic beta-cells. While type 1 is characterized by complete loss of beta-cells due to autoimmune attack on them, type 2 is characterized by a relative deficiency of betacells due to a decreased compensation for insulin resistance [1, 2]. Restoring beta-cell mass and reversing diabetes can be accomplished by two approaches: either by endogenous regeneration of beta-cells or transplantation of beta-cells from exogenous sources; recent advancements in science and technology have facilitated progress in both. In the first approach, while efforts to expand mature beta-cells in vitro have been met with limited success, regeneration of beta-cells from embryonic and adult stem cells, or pancreatic progenitor cells, has shown promise [2]. Understanding the role of beta-cell-specific transcription factors in the transdifferentiation to beta-cell phenotype is critical to further progress. Pharmacological approaches, employing growth factors, hormones, and small molecules, have also been shown to boost beta-cell proliferation and function. In the second approach, transplantation of isolated islets from cadaveric donor pancreas has proved to be an immediate and effective method for replacing depleted beta-cells in type 1 diabetic patients, allowing them to achieve independence from exogenous insulin administration [3, 4]. To preserve the transplanted beta-cell mass, however, islet transplant recipients require immunosuppression, which, under current regimens, are known to be beta-cell toxic. This limitation has ultimately led to poor long-term function of the transplanted islets and a disheartened medical community which is committed to providing a durable cure for patients.In this special issue, substantial developments made in different research areas aimed at overcoming current limitations of islet regeneration and transplantation are presented. Of the numerous papers received from this open submission format, selected papers have been recommended for publication after peer reviews. This special edition presents a collection of exciting papers that describe strategies to improve availability of beta-cells and islets for transplantation, and also to improve their posttransplant survival. It is clear that one of the major hurdles challenging further success in islet transplantation is the lack of suitable donor pancreases. This issue is compounded by poor longterm survival of allotransplanted islets. The review article by F.-C. Chou et al. summarizes many strategies developed to modulate immune response to transplanted islets. Gene therapy offers a powerful tool to engineer islet grafts to become resistant to apoptosis induced by inflammation and produce immunosuppressive molecules to attenuate T-cell response. In addition, the potential to develop patientspecific, autologous beta-cell replacement therapy by using iPSC-derived pancreatic beta-like cells is discussed. Key issues in this field which are presented in this paper include (i) duration and expression levels of targeted genes in islets,(ii) use of viral vectors for direct gene therapy that could lead to insertional mutagenesis and host immunogenicity,
影响因子：
5.8
作者：
Halban, Philippe A.;German, Michael S.;Weir, Gordon C.
通讯作者：
Weir, Gordon C.
DOI：
10.1111/j.1600-6143.2011.03977.x
发表时间：
2012-06
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Bellin MD;Barton FB;Heitman A;Harmon JV;Kandaswamy R;Balamurugan AN;Sutherland DE;Alejandro R;Hering BJ
通讯作者：
Hering BJ
影响因子：
5.8
作者：
Pipeleers, D.;Chintinne, M.;Gorus, F.
通讯作者：
Gorus, F.