Human Mesenchymal Stromal Cells Improve Survival and Function of Pancreatic Islets by Cell-to-Cell Contact
1Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and Medical Faculty, Geneva, Switzerland
2Institut d'Ingénierie Biologique et Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
3Division of Immunology and Allergy, Geneva University Hospitals and Medical Faculty, Geneva, Switzerland.
Meeting: 2015 American Transplant Congress
Abstract number: B290
Keywords: Islets, Xenotransplantation
Session Information
Session Name: Poster Session B: Vascularized Composite Tissue Allografts and Xenotransplantation
Session Type: Poster Session
Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background and Aim:
The aim of this study was to evaluate the survival and function of human pancreatic islets co-encapsulated with human Mesenchymal Stromal Cells (MSC) both in vitro and in vivo after transplantation in diabetic mice.
Methods:
Human MSC and islets (or pseudo-islets, obtained after digestion and reaggregation of islet cells) were coencapsulated in new hydrogel microspheres composed of calcium alginate and covalently crosslinked polyethylene glycol. Cell function was tested in vitro by static incubation for islets or pseudo-islets alone and together with MSC. Encapsulated cells were transplanted intraperitoneally in streptozotocin-induced diabetic mice. Islet function was evaluated by intraperitoneal glucose tolerance test (IPGTT). Grafts were retrieved after 15 days for morphological analysis.
Results:
In vitro, insulin secretion was significantly improved when MSC were in cell-cell contact with islets (or pseudo-islets) compared to islets that were only in paracrine contact with MSC (co-culture in dual chambers, p<0.05). Encapsulated islets alone reversed diabetes in mice after intra-peritoneal transplantation after 2 days and allowed to maintain normoglycemia up to 70 days, compared to free islets, that were rejected in 6±1 days (p<0.0001, Mantel Cox). Transplantation of co-encapsulated islets and MSC maintained normoglycemia in mice up to 90 days (p<0.05, Mantel Cox). IPGTT was performed at day 15 and mice transplanted with combined MSC-islets showed an improved glycemic response compared to mice with islets alone (p<0.001). Graft histology showed MSC located within and around the islets (or pseudo-islets), serving as stromal structure.
Conclusions:
MSC co-encapsulated with islets improve survival and function of endocrine cells by cell to cell contact.
To cite this abstract in AMA style:
Montanari E, Mahou R, Passemard S, Noverraz F, Morel P, Meier R, Bosco D, Seebach J, Wandrey C, Gerber S, Gonelle-Gispert C, Buhler L. Human Mesenchymal Stromal Cells Improve Survival and Function of Pancreatic Islets by Cell-to-Cell Contact [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/human-mesenchymal-stromal-cells-improve-survival-and-function-of-pancreatic-islets-by-cell-to-cell-contact/. Accessed November 21, 2024.« Back to 2015 American Transplant Congress