Current status and future of clinical islet xenotransplantation

Abstract

β-Cell replacement therapy, including allogeneic pancreas and islet transplantation, can normalize HbA1c levels in unstable type 1 diabetic (T1D) patients, but a donor shortage is a serious issue. To overcome this problem, xenotransplantation is an attractive option. In fact, islet transplantation from porcine pancreata was performed in the 1990s, which opened the door for islet xenotransplantation, but the possibility of porcine endogenous retrovirus (PERV) infection was raised, which has restricted progress in this field. The International Xenotransplantation Association published a consensus statement on conditions for undertaking clinical trials of porcine islet products in T1D to restart islet xenotransplantation safely. Clinical porcine islet xenotransplantation was restarted under comprehensive regulations in New Zealand. In addition, newly emerged gene-editing technologies have activated the xenotransplantation field. Islet xenotransplantation is becoming a clinical reality, with the results of recent studies showing promise to advance this field.

The effect of epitope‐based ligation of ICAM‐1 on survival and retransplantation of pig islets in nonhuman primates

“…Due to a severe shortage of donor pancreatic islets, much attention is currently being paid to xenotransplantation. 12 However, clinical application of islet xenotransplantation remains challenging because of the wide immunologic barrier between pigs and primates. Anti-CD154 mAb, which blocks co-stimulation through the CD154-CD40 pathway, has been used with various combinations of immunosuppressants in xenotransplantation experiments.…”

“…9 Currently, porcine islets are being intensively investigated in nonhuman primate (NHP) transplantation models. [10][11][12] The wide immunologic barrier between pigs and primates remains a main concern associated with graft failure. For the successful clinical application of islet xenotransplantation, novel immunosuppressive modalities are required, preferably an approach that induces tolerance to the graft in the recipient while preserving immune function against pathogenic microorganisms.…”

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

“…4 Islet xenotransplantation is becoming a clinical reality for DM therapy. 5 Postprandial glucose control, 6 C-peptide replacement 7 and phytomedicines intervention 8 have been explored for curing DM. Although these therapeutic approaches could alleviate the afflictions of patients with DM, they are unable to thoroughly cure DM.…”

Comparison of different compressed sensing algorithms for low SNR 19F MRI applications—Imaging of transplanted pancreatic islets and cells labeled with perfluorocarbons

“…For the most severe forms of Type I diabetes, caused by the loss of pancreatic beta cell mass or function, standard treatment using regular insulin administration is inadequate to achieve optimal regulation of the blood glucose levels. Transplantation of donor pancreatic islets becomes a potential treatment option for patients suffering from severe forms of Type I diabetes . However, clinical data shows that the outcome of islets transplantation is still insufficient and variable, despite multiple donor supplies and an improved immunosuppression regimen .…”

“…Transplantation of donor pancreatic islets becomes a potential treatment option for patients suffering from severe forms of Type I diabetes. 2 However, clinical data shows that the outcome of islets transplantation is still insufficient and variable, despite multiple donor supplies and an improved immunosuppression regimen. 3 Reliable non-invasive imaging for localization and quantification of pancreatic islets becomes necessary to monitor the fate of engrafted islets, to better understand mechanisms of islet degradation and further improve transplantation techniques.…”