Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans.

Raffaella Melzi, Paola Maffi, Rita Nano, Valeria Sordi, Alessia Mercalli, Marina Scavini, Antonio Secchi, Ezio Bonifacio, Lorenzo Piemonti

Research output: Contribution to journalArticle

Abstract

In this study we examined the effect of rapamycin (RAPA), a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function in vivo. Diabetic C57BL/6 or BALB/C recipient mice were transplanted with 350 syngeneic islets through the portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose concentrations and glucose tolerance were observed between RAPA- and vehicle-treated mice. The impact of RAPA on human islet engraftment was assessed in 10 patients with type 1 diabetes treated with : 0.1 mg/kg/day rapamycin before islet transplantation. Compared to non pre-treated islet transplant recipients (n = 12), RAPA pre-treated patients had increased blood RAPA concentrations (p = 0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post-transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2 and CCL3 concentrations pre-transplant (p <0.01), and a dampened chemokine response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the secretion of CCL2 and CCL3 by monocytes. Rapamycin does not adversely affect intrahepatic islet engraftment in the mouse, and potentially improves islet engraftment in humans by an anti-inflammatory mechanism.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalIslets
Volume1
Issue number1
Publication statusPublished - Jul 2009

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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