12 research outputs found
Previously published data showing overlap and correlation of islet equivalent dose with clinical transplant outcome.
<p>Data from Anazawa <i>et al</i>. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134428#pone.0134428.ref010" target="_blank">10</a>] illustrating that the <i>islet equivalent</i> (<i>IE</i>) <i>dose</i> correlates with the clinical outcome [insulin independence vs. dependence] at 6–12 months following islet autotransplant (IAT). However, the gray region indicates a wide range of <i>IE dose</i> (IE/kg of recipient) that is associated with an uncertain IAT outcome. The second graph shows the receiver operating characteristic (ROC) curve for this previously published data set with the area-under-the-curve (AUC) above.</p
Overlap and correlation of islet characterization methods with clinical transplant outcome.
<p>Data from our study illustrating that membrane integrity staining (based on FDA/PI), oxygen consumption rate (OCR) normalized to DNA content (OCR/DNA), and OCR/DNA normalized to the islet size index (ISI) (OCR/DNA/ISI) are not correlated with the clinical outcome [insulin independence vs. dependence] at 6–12 months following islet autotransplant (IAT). However, both <i>islet equivalent</i> (IE) <i>dose</i> and the <i>OCR dose</i> were correlated with post-IAT outcome. The gray region indicates the range of <i>IE</i> and <i>OCR doses</i> that is associated with uncertain IAT outcome. Note that the width of the gray region is much narrower with the <i>OCR dose</i>. The black dotted line represents the calculated cut-off point for clinical outcome (<i>IE dose</i>: 5,794 and <i>OCR dose</i>: 6.23). The second column of graphs represents receiver operating characteristic (ROC) curves for each of the five islet product characteristics from this data set. The area-under-the-curve (AUC) has been calculated for each islet product characteristic and these values are shown above each ROC curve.</p
Comparison of demographic, isolation, and quality assessment variables between insulin dependent and independent clinical transplant outcome 6–12 months post-transplant.
<p>Data are means ± standard error or percentage.</p><p><sup>a</sup>significant difference (p< 0.05) between groups as calculated by a Mann Whitney non-parametric test.</p><p>Comparison of demographic, isolation, and quality assessment variables between insulin dependent and independent clinical transplant outcome 6–12 months post-transplant.</p
Summary of cases where <i>OCR dose</i> correctly predicted clinical transplant outcome, whereas <i>IE dose</i> did not.
<p>Summary of cases where <i>OCR dose</i> correctly predicted clinical transplant outcome, whereas <i>IE dose</i> did not.</p
Barrier function of the membrane system for viral transmission.
<p>MRC-5 primary fibroblasts cultured in 24-transwell plates were separated from suspension containing reporter Lentiviruses by the membrane system for a period of 72 h. Infection rates were quantified by FACS analyses. Regardless of the MOI level, no relevant infection was detected in the membrane group (squares). In the control group (naïve membrane; circles), infection levels corresponded to increasing MOI levels from 40% up to 99.5%.</p
Function of macroencapsulated rat islet grafts.
<p>STZ-induced diabetic minipigs were transplanted with 6,730±475 IEQ/kg BW of rat islets immobilized and integrated into the macrochamber system. ivGTT was performed prior to graft implantation, 2 weeks after implantation, and after retrieval of the graft. BW was recorded daily throughout the observation period. (<b>A</b>) Fasting blood glucose levels (black) of group one transplanted minipigs (n = 5). The graft was removed on day 30 and hyperglycemia recurred demonstrating that graft function was responsible for normoglycemia during the implantation period. Rat C-peptide levels (grey) are presented as 4<sup>th</sup> grade polynomial curves. Error bars represent SD. <i>P</i><0.001 for comparing glucose levels during the implantation period vs the pre- and post-implantation periods (t-test). (<b>B</b>) Blood glucose levels during ivGTT of transplanted animals at two weeks (black circles) and after retrieval of the graft-containing device (black triangles). Diabetic minipigs (n = 24; double grey), naïve healthy mini-pigs (n = 11; black dashed) and naïve healthy rats (n = 36; grey dashed) served as controls. Error bars represent SD. <i>P</i><0.001 for comparing AUCs (diabetic minipigs) in the implantation period vs the pre- and post-implantation periods (t-test). (<b>C</b>) Two-day continuous glucose monitoring records of an implanted animal during week 2. (<b>D</b>) Fasting blood glucose levels (black) of group 2 transplanted minipigs (n = 3) and corresponding BW (grey). Normoglycemia was achieved rapidly after transplantation and was retained until the BW increased to a critical level of >160% of the initial BW. Data are presented as 5<sup>th</sup> grade polynomial curves. <i>P</i><0.001 for comparing glucose levels during the first 75 days of the implantation period vs the pre-implantation period (t-test).</p
Oxygen partial pressure in the gas chamber.
<p>Levels of oxygen at the end of successive 24 h cycles were monitored in the central cavity and in the 2 side chambers. Solid black line, central cavity; solid grey line, side chambers. Data are presented as the 3<sup>rd</sup> grade polynomial curves.</p
Determination of the barrier function of the chamber system.
<p>(<b>A</b>) Biopsies from alginate/islet slabs were taken at 30 days (left panel, slabs 1 and 2) and at 90 days (right panel, slab 3) to test for porcine DNA contamination inside the chamber. At both time points, no porcine DNA was detectable in any of the samples. Non-tissue samples were used as negative controls (NC). Tissue extracts from porcine muscle (M), spleen (S), and liver (L) served as positive controls (PC). (<b>B</b>) Serum samples of rat islet graft recipients were taken at various time points throughout the observation period of up to 90 days to test for development of anti-rat immunoglobulin. The 2 graphs show data of 2 individual recipients (left, 1709; right, 1736). Squares: positive control (sensitized animal); circles: negative control (healthy animal); triangles: diabetic minipig transplanted with encapsulated rat islets.</p
Chamber system for islet macroencapsulation.
<p>(<b>A</b>) Schematic view of the chamber composition. The core of the device is built as a gas module, connected to access ports for exogenous oxygen refueling. Active transport of solutes is achieved via a membrane impregnated with alginate (left, virgin; right, ready to use). Separated by gas permeable membranes, 2 compartments surround the central gas cavity that houses alginate-immobilized pancreatic islets. The plastic housing of the chamber has a latticelike design at both external surfaces and covered by hydrophylized PTFE porous membranes. (<b>B</b>) Photographic image of a completely assembled chamber with connected access ports. (<b>C</b>) X-ray image of an implanted recipient.</p
Blood markers in healthy, diabetic and device carrying mini-pigs.
<p>Data presented are mean ± standard deviation.</p><p>SGOT, serum glutamic oxaloacetic transaminase.</p