Pancreas and Islet Cell Transplantation

Sutherland, David E.R.; Gruessner, Angelika C.; Hering, Bernhard J.; Gruessner, Rainer W.G.

doi:10.1016/b978-0-323-02842-4.50047-4

Cited by 3 publications

(2 citation statements)

References 147 publications

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“…However, the stepwise blood glucose regulation granted by bolus injections of insulin is responsible for various detrimental complications manifested at later stages of life. Treatments that can yield physiologic glucose regulation, such as pancreas and islet transplantation, have recently shown significant promise2 although the limited availability of donor organs and the lifelong requirement of immunosuppressive medication remain significant unsolved problems in islet tissue replacement 3,4…”

Section: Introductionmentioning

confidence: 99%

Non‐Invasive Monitoring of a Bioartificial Pancreas in Vitro and in Vivo

Constantinidis

Long

Weber

et al. 2001

Annals of the New York Academy of Sciences

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Monitoring biochemical processes relevant to the function, survival, and longevity of tissue‐engineered pancreatic constructs is important for the development of an optimum construct design as well as patient care management after implantation. In this report we demonstrate the ability of nuclear magnetic resonance (NMR) techniques to monitor aspects of intracellular metabolism, overall morphology, and distribution of a microencapsulation based bioartificial pancreas in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

Non‐Invasive Monitoring of a Bioartificial Pancreas in Vitro and in Vivo

Constantinidis

Long

Weber

et al. 2001

Annals of the New York Academy of Sciences

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“…Thus, diabetogenic immunosuppressants need to be eliminated in order to allow optimal function of the engrafted islets. Immunosuppressants such as mycophenolate mofetil and rapamycin are expected to afford this possibility 10. Shapiro et al 11 were successful in treating seven consecutive diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Induction of Islet Allotolerance in Nonhuman Primates

Gaur

Nitta

Kennedy

et al. 2002

Annals of the New York Academy of Sciences

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Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after the second transplantation have shown trends towards normoglycemia in the presence of mycophenolate mofetil. All five animals that received the second transplant have shown an initial rise in C peptide levels, which rapidly decreased as we tapered the MMF dose from 20 mg/kg BID to 5 mg/kg SID. Two animals of the five that were preconditioned with MMF one week prior to transplantation have shown significantly higher C peptide levels. We believe that it is very important to understand the relationship between the first graft failure and subsequent islet allograft success. Since graft success did not correlate with number of transplanted islets, the correction of blood glucose levels toward normoglycemia after the second transplantation suggests a mechanism by which the allotolerance to second transplant is facilitated by the first islet transplantation. These initial observations suggest approaches to “tolerize” the recipient to accept the second‐transplant islets (a) through preconditioning the animal to improve the rate of success for the first transplant or (b) through tolerization to islets in the first transplant to facilitate better engraftment of the second‐transplant islets.

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Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

Sutherland

Radosevich

Bellin

et al. 2012

Journal of the American College of Surgeons

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Background Total-pancreatectomy (TP) with intraportal-islet-auto-transplantation (IAT) can relieve pain and preserve beta-cell-mass in patients with chronic-pancreatitis (CP) when other-therapies fail. Reported is a >30-year-single-center-series. Study Design 409 patients (53 children, 5–18 yrs) with CP underwent TP-IAT from Feb/1977–Sept/2011; (etiology idiopathic-41%; SOD/biliary-9%; genetic-14%; divisum-17%; alcohol-7%; other-12%); mean age-35.3 yrs,); 74% female; prior-surgeries 21%--Puestow procedure 9%, Whipple 6%, distal pancreatectomy 7%; other 2%). Islet-function was classified as insulin-independent for those on no insulin; partial if known C-peptide positive or euglycemic on once-daily-insulin; and insulin-dependent if on standard basal–bolus diabetic regimen. An SF-36-survey for Quality-of-Life (QOL)) was completed before and in serial follow-up by patients done since 2007 with an integrated-survey that added in 2008. Results Actuarial-patient-survival post-TP-IAT was 96% in adults and 98% in children (1-year) and; 89% and 98% (5-years). Complications requiring relaparotomy occurred in 15.9%, bleeding (9.5%) being most common. IAT-function is achieved in 90% (C-peptide >0.6 ng/ml). At 3 years, 30% were insulin-independent (25% in adults, 55% in children) and 33% had partial-function. Mean HbA1C was <7.0% in 82%. Prior pancreas surgery lowered islet-yield (2712vs4077/kg, p=.003). Islet yield [<2500/kg (36%); 2501–5000/kg (39%); >5000/kg (24%)] correlated with degree of function with insulin-independent rates at 3 yrs of 12, 22 and 72%, partial function 33, 62 and 24%. All patients had pain before TP-IAT and nearly all were on daily-narcotics. After TP-IAT, 85% had pain-improvement. By two years 59% had ceased-narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions including the Physical and Mental Component Summaries (P<0.01), whether on narcotics or not. Conclusions TP can ameliorate pain and improve QOL in otherwise-refractory-CP-patients, even if narcotic-withdrawal is delayed or incomplete because of prior long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in >2/3 of patients with insulin-independence occurring in one-quarter of adults and half the children.

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Pancreas and Islet Cell Transplantation

Cited by 3 publications

References 147 publications

Non‐Invasive Monitoring of a Bioartificial Pancreas in Vitro and in Vivo

Non‐Invasive Monitoring of a Bioartificial Pancreas in Vitro and in Vivo

Induction of Islet Allotolerance in Nonhuman Primates

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

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