Intraportal cotransplant of allogeneic donor MSCs + islets

Group 2 ID no.MHC class II matchbIEQ/kgDays off insulincDecrease in functiondDays C-peptide positive/POD necropsyDose DBMCsf/kg × 109Dose CD34/kg × 106POD 0 MSCs/kg × 106IV MSCsg/kg × 106POD chimhPeak level (%) chim
105-71haplo; hmz9,192899097/970.2535.31.25UDUD
35-493MM; hmz10,978106106181/1810.3060.41.45.8UDUD
  • Animals received induction treatment with four doses of 10 mg/kg thymoglobulin given in the week prior to transplant, and four doses of 50 mg/m2 fludarabine. IM rapamycin were initiated 1–5 days prior to intraportal islet/donor MSC transplant on POD 0, with a goal of achieving trough levels of 15–20 ng/ml in all animals, except for 105-131, 26-20, and CW1H, in which rapamycin treatment started on POD 14. These three animals were also treated with anti-CD154. Chimerism was measured using 6 class II based primer and probe sets for donor DNA.

  • aAnti-CD154 rx.

  • bMM, recipient and donor are MHC class II mismatched; haplo, MHC class II haploidentical; hmz, homozygous recipient.

  • cNot necessarily consecutive to islet transplant.

  • dOn the basis of blood glucose levels, insulin requirement, and/or C-peptide.

  • eAnimal expired CMV positive.

  • fDBMCs were debulked with a CD11b bead-based method and given intravenously on PODs 4 or 5 and 11.

  • gMSCs given intravenously on PODs 5 and 11.

  • hChimerism, monitored twice per month, determined using 6 class II based primer probe sets for donor DNA; the lower limit of detection ranged from 0.03 to 0.1%, depending on the primer probe set. UD, undetectable.