Update on Islet Transplantation

McCall, Michael; Shapiro, A.M. James

doi:10.1101/cshperspect.a007823

Cited by 190 publications

(150 citation statements)

References 92 publications

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“…Even though β cell replacement strategies can be effective in principle, they are limited by β cell availability (McCall and Shapiro, 2012), necessitating the identification of novel exogenous or endogenous sources of therapeutic β cells. Here, we have exploited a zebrafish model of conditional β cell ablation, in which functional β cell mass rapidly recovers, to study mechanisms of vertebrate β cell regeneration.…”

Section: Discussionmentioning

confidence: 99%

glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis

et al. 2015

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The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model of beta cell ablation, we demonstrate conserved plasticity of alpha cells during islet regeneration. In addition, we show that glucagon expression is upregulated after injury. Through gene knockdown and rescue approaches, we also find that peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate switching. Importantly, whereas beta cell neogenesis was stimulated by glucose, alpha-to-beta cell conversion was not, suggesting that transdifferentiation is not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall, this study supports the hypothesis that alpha cells are an endogenous reservoir of potential new beta cells. It further reveals that glucagon plays an important role in maintaining endocrine cell homeostasis through feedback mechanisms that govern cell fate stability.

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Section: Discussionmentioning

confidence: 99%

glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis

et al. 2015

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“…[59] Her ne kadar yöntem gelitirilmi olsa da donör sayısın-daki azlık, elde edilen hücre sayısında yetersizlik ve alıcının uzun süre boyunca immün sisteminin baskılanması, söz konusu yöntemin kullanılılı¤ını azaltmaktadır. [60][61][62] Günümüzde halen diyabet tedavisine yönelik MKH nakli çalımaları deneysel aamadadır ve çeitli kök hücre tiplerinde yapılan aratırmalara göre CD34 + kemik ili¤i ve kordon kanı kök hücreleri, di¤er kaynaklardan elde edilen mezenkimal hücrelere oranla daha iyi sonuçlar vermitir. [63,64] Lakin elde edilen sonuçlar, metabolik ileyii çok yönlü olan diyabet için tam anlamıy-la yeterli görülmemekte, çeitli fizyolojik unsurlar de¤erlendirilerek daha çok veri ile karılatırılması gerektirmektedir.…”

Section: Self-renewal (Kendini Yenileyebilme)unclassified

Stem cells; mesenchymal stem cells and current clinical applications

Tekeli¹

2016

FNG & Bilim Tıp Transplantasyon Dergisi

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Stem cells are defined as a type of cell that have the features of self-renewal, unlimited proliferation capacity, potential of differentiation into other cell types and ability to repair damaged structure when given to damaged tissue. Stem cells are preferred for regenerative medical applications because of their abundance, being easily obtained, ability to proliferate by differentiating into many cell types and being transplantable safely and effectively to recipients. In this review, we introduce mesenchymal stem cells as one of the most important sources of stem cells that have clinical applications and give examples of their usage areas in the clinic and of studies.Keywords: Clinical application; mesenchymal stem cells; stem cell. Stem cells; mesenchymal stem cells and current clinical applications ÖZKök hücreler; kendilerini yenileyebilme, sınırsız çoğalabilme, kendilerinden başka hücrelere farklılaşabilme, hasarlı dokuya verildiğinde hasarlı yapıyı onarabilme özellikleri ile tanımlanan hücre tipidir. Kök hücreler bol miktarda bulunmaları, kolay elde edilebilmeleri, birçok hücre tipine farklılaşarak çoğalabilmeleri, alıcılara güvenli ve etkin bir şekilde nakledilebilmeleri nedeniyle rejeneratif tıp uygulamalarında tercih edilmektedir. Bu derlemede, klinikte uygulamaları bulunan ve en önemli kök hücre kaynaklarından biri olan mezenkimal kök hücreler tanıtılacak, klinikteki kullanım alanları ve çalışmalardan örnekler verilecektir.

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“…Using the Edmonton protocol, involving a glucocorticoid-free immunosuppressive regimen, insulin independence was achieved in most patients, giving great hope to the field [15]. However, an international trial using that protocol did not have equivalent success [16], perhaps related to differences in sites in experience both with the complex preparation of human islets for transplantation and clinical experience in the routine management of immunosuppressive therapies [17]. Nonetheless, there has been a progressive improvement in outcomes [18], and the Clinical Islet Transplantation Consortium has completed a Phase III trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycaemia [19].…”

Section: Islet Replacement Therapy: Realitymentioning

confidence: 99%

Hope vs hype: where are we in type 1 diabetes?

Skyler

2017

Diabetologia

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Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function. Mechanical replacement of islet cell function involves the use of glucose sensor-controlled insulin infusion systems. As all of these avenues are pursued, headlines often overstate the case, thus hyping any given advance, which provides enormous hope for patients and families seeking a cure for type 1 diabetes. Often, however, it is an animal study or a pilot trial that is being described. The reality is that translation to successful trials in human beings may not be readily achievable. This article discusses both the hype and the hopes in type 1 diabetes research.

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Update on Islet Transplantation

Cited by 190 publications

References 92 publications

glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis

glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis

Stem cells; mesenchymal stem cells and current clinical applications

Hope vs hype: where are we in type 1 diabetes?

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