Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine, mycophenolate mofetil, and leflunomide remain normoglycemic for up to 100 days

Wennberg, Lars; Song, Z.; Zhang, J; Bennet, William; Nava, Stefano; Bari, S; Sundberg, Berit; Korsgren, Olle; Groth, Carl G.

doi:10.1016/s0041-1345(00)01119-2

Cited by 33 publications

(63 citation statements)

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“…Adult porcine islets (APIs) were isolated from porcine pancreases using a semiautomatic technique, as described previously (11). The islets were cultured in M199 culture medium (GIBCO, BRL, Life Technologies Ltd., Paisley, Scotland, UK) supplemented with 10% porcine serum (GIBCO, BRL), 1 mM calcium nitrate, 0.02 lM selenium, 20 mM nicotinamide (NIC) (Sigma Chemicals, St. Louis, MO, USA), 25 mM N-2-hydroxyethylpiperazine-N 1 -2-ethanesulfonic acid (HEPES) (GIBCO, BRL), fungizone (500 lg/L) (GIBCO, BRL) and gentamicin (50 mg/L) (GIBCO, BRL).…”

Section: Adult Porcine Islet Isolationsmentioning

confidence: 99%

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The ADP/ATP Ratio: A Novel Predictive Assay for Quality Assessment of Isolated Pancreatic Islets

Goto

Holgersson

Kumagai‐Braesch

et al. 2006

American Journal of Transplantation

106

101

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The current standard assays for islet product release criteria are unable to predict the outcome after clinical islet transplantation. Therefore, establishment of reliable and rapid assays enabling pre-transplantation prediction of islet potency is warranted. In the present study, we have evaluated the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) test, the glucose-stimulated insulin release, the loss of islets during the first 24 h in culture, and the insulin/deoxyribonucleic acid as predictive assays for the ability of isolated porcine islets to cure athymic mice with streptozotocin-induced diabetes. From the results presented, it is concluded that the measurement of the ADP/ATP ratio was the only test that correlated with transplantation outcome. In summary, we propose that the ADP/ATP assay is worthwhile as applied to human islet transplantation and seek to validate it as a rapid and potent predictor of transplant outcome.

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Section: Adult Porcine Islet Isolationsmentioning

confidence: 99%

“…The insulin/DNA ratio in the APIs was measured as previously described (11) and expressed as pmol/lg.…”

Section: In Vitro Evaluation Of Pig Islet Qualitymentioning

confidence: 99%

The ADP/ATP Ratio: A Novel Predictive Assay for Quality Assessment of Isolated Pancreatic Islets

Goto

Holgersson

Kumagai‐Braesch

et al. 2006

American Journal of Transplantation

106

101

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“…In previous studies that did not employ transplantation of E28 pig pancreatic primordia prior to implantation of islets or islet cell clusters [14][15][16] complete destruction of grafts was evident within two weeks. Pre-immunization of rats by subcutaneous injection of porcine islet cell clusters accelerates the rejection of islet probes.…”

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confidence: 92%

Organogenetic tolerance

Hammerman

2010

Organogenesis

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“…Mycophenolate mofetil (CellCept), a prodrug of MPA, induces activated Tlymphocyte apoptosis by depleting the dGTP pool required for DNA synthesis (Allison & Eugui 2000) and has been shown to induce long-term tolerance alone (Hao et al 1990, Wennberg et al 2001 or in combination with other immunosuppressive drugs including Tac (Jones et al 1999). Tac prevents interleukin-2 production by antigen-activated T-cells through inhibition of T-cellspecific and non-specific transcription factors required for the activation of interleukin-2 gene expression (Siekierka et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies

Asfari

Berta²,

Coffy³

et al. 2005

Journal of Endocrinology

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One of the major requirements for a successful and life-lasting organ transplant is the access to safe, least toxic and permanent tolerance-inducing drugs. In this study we wished to evaluate the effects of tolerogenic doses of the immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal -cell lines, both in vivo and in vitro. Here we demonstrate that combined administration of low-dose MPA and Tac for 23 days induced permanent tolerance in an allogeneic -cell line transplant in Wistar rat liver through the portal vein. This short-term treatment of tolerogenic doses of the two drugs was deleterious to the survival of the transplanted cells but a small percentage of the cells could resist the effect and become fully active when the drugs were removed. The surviving cells, retrieved from growth in vivo, did not exhibit increased resistance in comparison to the original cells when tested in vitro at two glucose concentrations, 10 and 20 mM. The presence of a small percentage of resistant cells at the two glucose concentrations was also detected in the in vitro study after a continuous 8-day treatment demonstrating that the in vivo resistance was not related to micro-environmental protection but possibly to a phenotypic cell state that is yet to be determined.

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Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine, mycophenolate mofetil, and leflunomide remain normoglycemic for up to 100 days

Cited by 33 publications

References 1 publication

The ADP/ATP Ratio: A Novel Predictive Assay for Quality Assessment of Isolated Pancreatic Islets

The ADP/ATP Ratio: A Novel Predictive Assay for Quality Assessment of Isolated Pancreatic Islets

Organogenetic tolerance

Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies

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