Histologic Graft Assessment After Clinical Islet Transplantation

Toso, Christian; Isse, Kumiko; Demetris, Anthony J.; Dinyari, Parastoo; Koh, Angela; Imes, Sharleen; Kin, Tatsuya; Emamaullee, Juliet; Senior, Peter; Shapiro, A. M. James

doi:10.1097/tp.0b013e3181bc06b0

Cited by 74 publications

(59 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clear histological evidence of recurrent autoimmunity with selective b-cell destruction after islet transplantation has been shown by Rossini's group (Rossini 2004;Sharma et al 2006). Although core biopsy of an intrahepatic islet transplant is technically possible, the approach is unattractive to patients, and only yields islet material in about half of the cases (Toso et al 2009). However, encouraging data is beginning to emerge from sequential analysis of peripheral blood.…”

Section: Update On Islet Transplantationmentioning

confidence: 99%

See 1 more Smart Citation

Update on Islet Transplantation

McCall

Shapiro²

2012

Cold Spring Harbor Perspectives in Medicine

190

148

View full text Add to dashboard Cite

Clinical islet transplantation has progressed considerably over the past 12 years, and .750 patients with type 1 diabetes have received islet transplants internationally over this time. Many countries are beginning to accept the transition from research to accepted and funded clinical care, especially for patients with brittle control that cannot be stabilized by more conventional means. Major challenges remain, including the need for more than one donor, and the requirement for potent, chronic immunosuppression. Combining immunological tolerance both to allo-and autoantigens, and a limitless expandable source of stem cell-or xenograft-derived insulin-secreting cells represent remaining hurdles in moving this effective treatment to a potential cure for all those with type 1 or 2 diabetes.

show abstract

Section: Update On Islet Transplantationmentioning

confidence: 99%

“…Random biopsy sampling is only successful in 30% of attempts and may not provide timely answers as samples are prepared and analyzed (Toso et al 2009). Imaging modalities may provide a more timely answer to posttransplant islet status.…”

Section: The Portal Sitementioning

confidence: 99%

Update on Islet Transplantation

McCall

Shapiro²

2012

Cold Spring Harbor Perspectives in Medicine

190

148

View full text Add to dashboard Cite

show abstract

“…Various tests have been due to recurrence of autoimmune diabetes. Here again, ex vivo blood-based monitoring strategies have been esassessed, including the use of positron emission tomography (PET) (14,38), magnetic resonance imaging (MRI) tablished, and patients with type 1 diabetes have higher levels of lymphocyte reactivity against islet-specific (26,37), liver biopsy (34), and immunological markers (PCR for granzyme B and/or insulin mRNA, soluble peptides and proteins than control individuals (25,31). This study was designed to assess the feasibility and CD30, flow cytometry) (5,16,19,32).…”

Section: Introductionmentioning

confidence: 99%

Detecting Rejection after Mouse Islet Transplantation Utilizing Islet Protein-Stimulated ELISPOT

et al. 2011

Self Cite

View full text Add to dashboard Cite

Improved posttransplant monitoring and on-time detection of rejection could improve islet transplantation outcome. The present study explored the possibility of detecting harmful events after mouse islet transplantation measuring the immune responsiveness against islet extracts. Mouse islet transplantations were performed using various donor/recipient combinations, exploring autoimmune (NOD/SCID to NOD, n = 6) and alloimmune events (C57BL/6 to BALB/c, n = 20), a combination of both (C57BL/6 to NOD, n = 8), the absence of both (BALB/c to BALB/c, n = 21), or naive, nontransplanted control mice (n = 14). The immune reactivity was measured by ELISPOT, looking at the ex vivo release of IFN-γ from splenocytes stimulated by islet donor extracts (sonicated islets). The immune reactivity was not altered in the syngeneic and autoimmune models, demonstrating similar levels as nontransplanted controls (p = 0.46 and p = 0.6). Conversely, the occurrence of an allogeneic rejection alone or in combination to autoimmunity was associated to an increase in the level of immune reactivity (p = 0.023 and p = 0.003 vs. respective controls). The observed increase was transient and lost in the postrejection period or after treatment with CTLA4-Ig. Overall, allogeneic rejection was associated to a transient increase in the reactivity of splenocytes against islet proteins. Such a strategy has the potential to improve islet graft monitoring in human and should be further explored.

show abstract

“…Current tools for the immune monitoring of islet cell grafts usually allow identification of graft dysfunction when it is too late to take action, and therefore, cannot be used to guide clinical intervention (2,6). A reliable, noninvasive, real-time monitoring tool is needed to allow for earlier and more accurate detection of harmful events.…”

Section: Methodsmentioning

confidence: 99%

“…Long incubation times and low correlation with the clinical outcome are some of the disadvantages related to the T cell-based assays (2). Tissue biopsy is the standard method for accessing immune cell infiltration in the graft, but the method is both invasive and inadequate when temporal information is needed to characterize the immune reaction that progresses dynamically over time (6). Noninvasive assessment of this damage would greatly aid in monitoring recurrent posttransplant events and in devising therapeutic interventions.…”

Section: Molecular Imaging: Rejection Of Pancreatic Islet Cell Transpmentioning

confidence: 99%

Immune Rejection after Pancreatic Islet Cell Transplantation: In Vivo Dual Contrast-enhanced MR Imaging in a Mouse Model

Wang¹,

Schuetz²,

Ross³

et al. 2013

Radiology

View full text Add to dashboard Cite

Purpose:To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a longcirculating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium-diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption. Materials and Methods:All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 3 10 6 splenocytes from 6-weekold nonobese diabetic mice. These mice also served as control subjects for comparison of pre-and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance. Results:MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec 6 39.3 and 239.5 msec 6 17.6, respectively; P , .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium. Conclusion:PGC-Gd-DTPA-F-enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl

show abstract

Histologic Graft Assessment After Clinical Islet Transplantation

Cited by 74 publications

References 33 publications

Update on Islet Transplantation

Update on Islet Transplantation

Detecting Rejection after Mouse Islet Transplantation Utilizing Islet Protein-Stimulated ELISPOT

Immune Rejection after Pancreatic Islet Cell Transplantation: In Vivo Dual Contrast-enhanced MR Imaging in a Mouse Model

Contact Info

Product

Resources

About