Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia

Mario G. Solari, Suganya Srinivasan, Imene Boumaza, Jignesh Unadkat, George Harb, Adolfo Garcia-Ocana, Maryam Feili-Hariri

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Allogeneic islet transplantation is an option to treat diabetes however there are obstacles that are limiting its clinical use. We have examined whether mesenchymal stem cells (MSC) improve islet graft survival and whether such therapy allows for better graft acceptance with reduced requirement for immunosuppression. In vitro-expanded syngeneic bone marrow-derived MSC were co-transplanted with islets into omental pouch in a rat model of streptozotocin-induced diabetes. Marginal mass syngeneic islet transplantation into the omentum with MSC promoted sustained normoglycemia. Interestingly, allogeneic islets +MSC, but not islets alone, with short-term use of immunosuppression enhanced long-term islet graft survival, insulin expression in the grafts and induced normal serum insulin levels and normoglycemia. T cells from recipients transplanted with allogeneic islets +MSC produced low levels of IFN-γ and TNF-α upon ex-vivo activation, and this transplantation protocol promoted the generation of IL-10-secreting CD4+ T cells. These data encourage further preclinical and eventually, clinical MSC-based islet transplantation to improve the outcome of allogeneic islet transplantation in the treatment of diabetes.

Original languageEnglish
Pages (from-to)116-124
Number of pages9
JournalJournal of Autoimmunity
Volume32
Issue number2
DOIs
StatePublished - Mar 2009
Externally publishedYes

Keywords

  • Islet transplantation
  • Mesenchymal stem cells
  • Omentum
  • Rat
  • Th1 suppression

Fingerprint

Dive into the research topics of 'Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia'. Together they form a unique fingerprint.

Cite this