Mesenchymal Stem Cells Enhance Rejection Free and Overall Islet Allograft Survival
1Surgery, University of Miami School of Medicine, Miami, FL
2Surgery, University of Illinois at Chicago, Chicago, IL
3National Center for Supercomputing and Analysis, University of Illinois at Urbana-Champaign, Urbana-Champaign, IL
4Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
Meeting: 2015 American Transplant Congress
Abstract number: 368
Keywords: Graft survival, Islets, Major histocompatibility complex (MHC), Stem cells
Session Information
Session Name: Concurrent Session: Islet Transplantation: Basic
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 3:15pm-3:27pm
Location: Room 121-C
The purpose of this study was 1) to assess the effect of mesenchymal stem cells (MSC) on intrahepatic, allogeneic islet survival in a cynomolgus monkey (cyno) model and 2) to determine the effect of the MSC MHC on outcome. METHODS. Islet donor-recipient pairs were ABO compatible and MHC mismatched. Diabetes was induced with streptozotocin and recipients were immunosuppressed with thymoglobulin (10 mg/kg) on post-operative day (POD) -1, 0, 2 and 4, tacrolimus from POD -1 through 30, and rapamycin from POD 28 on (target trough levels of 8-10 and 8-12 ng/ml, respectively). Islets were transplanted on POD 0 with no MSC (control, n=6), 1×106MSC/kg into the liver with islets on POD 0 only (POD 0, n=7) or additional IV MSC on POD 5, 11, 18 and 28 at 2×106MSC/kg (Multiple, n=8). MSC were derived from recipient, donor or 3rd party bone marrow, and passage 4 MSC were utilized for transplant. Duration of rejection free and overall islet survival was determined via analysis of fasting and post-prandial blood glucose and fasting c-peptide. Pre and post transplant peripheral blood samples were collected and analyzed for metabolic, immunologic and genomic parameters. RESULTS. For the Multiple group, 100% remained rejection free through POD 60 vs 33.3% and 14.3% for control and POD 0 groups, respectively (p<0.001 log-rank test). At POD 120, 62.5% of the Multiple group was rejection free as compared to 33.3% and 0% for control and POD 0 groups, respectively (p<0.002). Overall islet allograft survival at POD 120 was 87.5% for the Multiple vs 33.3% and 14.3% for control and POD 0 groups, respectively (p<0.002). Anti-class II specific alloantibodies were detected for all groups; anti-donor MLR was decreased during periods of graft stability and increased subsequent to rejection. CONCLUSIONS. A significant increase in rejection free and overall islet allograft survival was observed for recipients of multiple MSC infusions. Adequate numbers of MSC were readily produced and multiple infusions appeared safe and well tolerated.
To cite this abstract in AMA style:
Kenyon N, Willman M, Dongmei H, Ana H, Rabassa A, Diaz W, Geary J, Kenyon N, Bartholomew A, McHenry K, Salomon D, Berman D. Mesenchymal Stem Cells Enhance Rejection Free and Overall Islet Allograft Survival [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/mesenchymal-stem-cells-enhance-rejection-free-and-overall-islet-allograft-survival/. Accessed May 9, 2025.« Back to 2015 American Transplant Congress