Allosensitization of Islet Allograft Recipients

Cardani, Roberta; Pileggi, Antonello; Ricordi, Camillo; Gómez, Carmen; Baidal, David; Ponte, Gaston; Mineo, Davide; Faradji, Raquel N.; Froud, Tatiana; Ciancio, Gaetano; Esquenazi, Violet; Burke, George W.; Selvaggi, Gennaro; Miller, Joshua; Kenyon, Norma S.; Alejandro, Rodolfo

doi:10.1097/01.tp.0000290388.70019.6e

Cited by 68 publications

(65 citation statements)

References 48 publications

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Section: Bone Marrow Stem Cell Transplantation To Induce Hematopoietimentioning

confidence: 99%

“…The remaining patients maintained kidney function without rejection episodes during the follow-up period. Development of cytotoxic anti-donor MHC antibodies occurred in six patients, but it was not associated with loss of kidney graft function [43]. A subsequent ITA trial (year 1998) in patients with T1D (n = 5) involved intra-hepatic transplantation of allogeneic islets, combined with intravenous infusion of enriched CD34 + BMSC on days 5 and 11 after islet transplantation.…”

Section: Bone Marrow Stem Cell Transplantation To Induce Hematopoietimentioning

confidence: 99%

See 1 more Smart Citation

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Fotino

Ricordi²,

Lauriola

et al. 2010

Rev Diabet Stud

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■ AbstractThe bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMSC) transplantation (BMT) may assist in achieving tissue repair and regeneration, and in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMSC to preserve functional beta-cell mass in subjects with type 1 and type 2 diabetes, and to favor engraftment and survival of transplanted islets. Additional trials are evaluating the impact of BMT (i.e., mesenchymal stem cells) on the progression of diabetes complications. This article reviews the progress in the field of BMSC for the treatment of subjects with insulindependent diabetes, by combining allogeneic islet transplantation with donor-specific BMSC. Clinical data is summarized from pilot studies performed at our research center over the last two decades.

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Section: Bone Marrow Stem Cell Transplantation To Induce Hematopoietimentioning

confidence: 99%

Section: Bone Marrow Stem Cell Transplantation To Induce Hematopoietimentioning

confidence: 99%

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Fotino

Ricordi²,

Lauriola

et al. 2010

Rev Diabet Stud

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“…Second, islet transplantation features an especially complex immunological situation. Patients transplanted with donor islets may develop allotype immunization (2), which could complicate future transplants. Furthermore, the life-long use of immunosuppressive therapy is essential for controlling alloimmunity and ideally also autoimmunity.…”

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confidence: 99%

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Ludwig

Rotem

Schmid

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

169

129

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Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing β-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation. treatment of diabetes | immune isolation | beta cells

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“…Negative cross-match, recipient panel reactive antibodies (PRA) ≤20%, ABO/Rh and CMV serology but not HLA compatibility, were required (22).…”

Section: Recipient Selection and Organ Procurementmentioning

confidence: 99%

Combined Islet and Hematopoietic Stem Cell Allotransplantation: A Clinical Pilot Trial to Induce Chimerism and Graft Tolerance

Mineo

Ricordi

et al. 2008

American Journal of Transplantation

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To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 ± 2113 IEQ/kg) followed by high doses of donor HSC (4.3 ± 1.9 × 10 6 HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFa antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 ± 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 ± 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 ± 0.48%), highly reduced at 1-year (0.20 ± 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.

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Allosensitization of Islet Allograft Recipients

Cited by 68 publications

References 48 publications

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Combined Islet and Hematopoietic Stem Cell Allotransplantation: A Clinical Pilot Trial to Induce Chimerism and Graft Tolerance

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