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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EResults from recent \u003Cem\u003Ein vivo\u003C\/em\u003E studies suggest that transplanted islet cells that are derived from human embryonic stem cells can provide stable, lasting glucose control. This article discusses not only the efficacy of such an approach but also the means to sustain the transplant without suppressing the patient\u0027s immune system.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eendocrinology\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EResults from recent \u003Cem\u003Ein vivo\u003C\/em\u003E studies suggest that transplanted islet cells that are derived from human embryonic stem cells (hESCs) can provide stable, lasting glucose control. In a session titled, \u201cNew Hopes for Stem Cells,\u201d Emmanuel Baetge, PhD, Chief Science Officer, Novocell, San Diego, CA, discussed not only the efficacy of such an approach but also the means to sustain the transplant without suppressing the patient\u0027s immune system.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe International Diabetes Federation estimates that there are over 246 million patients who are currently diagnosed with either type 1 or type 2 diabetes, a figure that is expected to balloon to 380 million cases by the year 2030. To date, the treatment of diabetes has been the straightforward maintenance of blood glucose homeostasis by the direct administration of insulin or by other pharmacologic means. However, such interventions do not address the underlying problem of dysfunctional pancreatic islet beta-cells and imperfectly controlled blood glucose levels. The ideal solution, therefore, is long-term islet cell protection or, failing this, islet replacement.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003E\u201cType 1 and 2 diabetes is a beta-cell mass disease,\u201d said Dr. Baetge. \u201cThe question for replacement is can we substitute primary islets with something that comes from a stem cell?\u201d Driving this question is the fact that primary islets, such as the source that was used in the Edmonton Protocol, are harvested from human donors; this approach requires life-long immune suppression for the recipient, and the cell source is not amenable to scale-up.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDirected Differentiation\u003C\/h2\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe use of hESCs in this, or any, setting is predicated on the ability to produce the type of cell that is required, and for Dr. Baetge, this entailed the \u201crecapitulation of embryonic development required for pancreatic islet cell formation.\u201d In order to drive the \u003Cem\u003Etabula rasa?\u003C\/em\u003E hESC to eventual beta-cell production, the first step is differentiation into the definitive endoderm, the progenitor of the pancreas and liver, among other cell types. The ability to do this with hESCs was first demonstrated by the Novocell team in 2005 (D\u0027Amour et al. \u003Cem\u003ENature Biotechnology\u003C\/em\u003E 2005).\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EShortly following this, the methods of differentiation to produce pancreatic endoderm and then pancreatic endocrine cells were established (D\u0027Amour et al. \u003Cem\u003ENature Biotechnology\u003C\/em\u003E 2006); the therapeutic function of these cells was demonstrated in April of this year (Kroon et al. \u003Cem\u003ENature Biotechnology 2008\u003C\/em\u003E). In this study, mice were first implanted with the pancreatic islet progenitor cells that gave rise to glucose-responsive human C peptide-secreting islet cells over 60 to 90 days. The animals were then exposed to streptozotocin, an agent that is selectively toxic to rodent but not human insulin-producing islet cells. The STZ-treated animals remained nondiabetic after STZ destruction of the endogenous mouse beta-cells. Using C-peptide as a surrogate marker for insulin, as well as blood glucose levels, researchers showed that the implant was able to maintain glucose homeostatis, and further, islet grafts that were maintained out to 120 days exhibited all the properties of functional beta-cells. \u201cThe development of these cells \u003Cem\u003Ein vivo\u003C\/em\u003E is replicating what you\u0027d expect in normal biology,\u201d said Dr. Baetage. Glucose control was lost when the implant was removed.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAs this approach comes closer to clinical implementation, 2 issues still require resolution\u2014first, the enrichment of cell product for the desired cell type (regardless of the method, other cell types will inevitably be present, which are allowed as long as they are safe), and second, protecting the implant against the patient\u0027s immune system. For purity, optimized differentiation and enrichment strategies can achieve a progenitor cell population that is greater than 80% enriched. For stable delivery without immunosuppression, Novocell currently is evaluating its own polyethylene glycol hydrogel coating system in addition to other retrievable encapsulation systems. Successful encapsulation requires good biocompatibility for subcutaneous placement, protection of implanted cells from immune rejection, and facilitation of the appropriate vascularization for maintenance of islet cell function and health.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/7\/28.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmci1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}