ArticleTransplantation2013
Novel sphingosine-1-phosphate receptor modulator KRP203 combined with locally delivered regulatory T cells induces permanent acceptance of pancreatic islet allografts.
Article in Transplantation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The novel sphingosine-1-phosphate receptor modulator KRP-203 prevents myocardial ischemia-reperfusion injury by preserving mitochondrial function through activation of the RISK and SAFE signaling pathways.Cell biology and toxicology · 2025Article
- Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells.Biochemical and biophysical research communications · 2023Article
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft.Frontiers in immunology · 2022Article
- Role of sphingosine-1-phosphate receptors in vascular injury of inflammatory bowel disease.Journal of cellular and molecular medicine · 2021Review
- A Multicentre, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of the S1P Receptor Agonist KRP203 in Patients with Moderately Active Refractory Ulcerative Colitis.Inflammatory intestinal diseases · 2020Article
- The S1P-S1PR Axis in Neurological Disorders-Insights into Current and Future Therapeutic Perspectives.Cells · 2020Review
- Ceramide and Sphingosine 1-Phosphate in Liver Diseases.Molecules and cells · 2020Review
- Short-term KRP203 and posttransplant cyclophosphamide for graft-versus-host disease prophylaxis.Bone marrow transplantation · 2020Article
- Tregs and Mixed Chimerism as Approaches for Tolerance Induction in Islet Transplantation.Frontiers in immunology · 2020Review
- S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy.Molecular diagnosis & therapy · 2019Review
- Engineering immunomodulatory biomaterials for type 1 diabetes.Nature reviews. Materials · 2019Article
- Drug repurposing: Ibrutinib exhibits immunosuppressive potential in organ transplantation.International journal of medical sciences · 2018Article
- Sphingosine 1-Phosphate Signaling as a Target in Hepatic Fibrosis Therapy.Frontiers in pharmacology · 2017Review
- Transplantation of xenogeneic islets: are we there yet?Current diabetes reports · 2013Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKRP203, a structural FTY720 analogue, has 5-fold greater selectivity for binding to sphingosine-1-phosphate receptor (S1PR) 1 (S1PR(1)) versus S1PR3 and 100-fold greater selectivity over S1PR(2) and S1PR(5). Although the immunoregulatory effects of FTY720 have been tested in clinical and experimental research, the therapeutic efficacy of KRP203 in allograft models remains elusive. In this study, we investigated the potential of KRP203 alone and in combination with intragraft injection of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) to induce islet allograft tolerance.
methodsBALB/c (H-2(d)) mice received transplants of fresh C57BL/10 (H-2(b)) islet allografts under the kidney capsule and were treated for 7 days with 0.3, 1.0, or 3.0 mg/kg KRP203 alone or in combination with intragraft-infused Tregs.
resultsUntreated BALB/c mice acutely rejected C57BL/10 islet allografts at a mean survival time of 13.8 ± 2.7 days (n=5). A 7-day dosing of 0.3 or 1.0 mg/kg KRP203 produced long-term islet allograft survival (9200 days) in one of five and two of seven recipients, respectively. A 3 mg/kg KRP203 dose resulted in islet graft survival for more than 200 days in 5 of 12 recipients. Whereas recipients that received 500 allogeneic islets admixed with 5 x 10(5) - 7 x 10(5) Tregssurvived 83.6 ± 67.2 days, addition of transient 3 mg/kg KRP203 therapy induced prolonged drug-free graft survival (9200 days) in all recipients.
conclusionsA brief treatment with KRP203 significantly prolonged islet allograft survival, whereas additional intragraft delivery of Tregs induced tolerogenic effects selective to islet alloantigens.
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