Co-graft of allogeneic immune regulatory neural stem cells (NPC) and pancreatic islets mediates tolerance, while inducing NPC-derived tumors in mice

PLoS One. 2010 Apr 27;5(4):e10357. doi: 10.1371/journal.pone.0010357.


Background: Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.

Methodology/principal finding: Diabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP(+) NPC from fully mismatched C57BL/6 mice. The following 4 groups of recipients were used: mice receiving islets alone; mice receiving islets alone and treated with standard immunosuppression (IL-2Ralpha chain mAbs + FK506 + Rapamycin); mice receiving a mixed islet/NPC graft under the same kidney capsule (Co-NPC-Tx); mice receiving the islet graft under the left kidney capsule and the NPC graft under the right kidney capsule (NPC-Tx). Our results demonstrate that only the co-transplantation and co-localization of NPC and islets (Co-NPC-Tx) induce stable long-term graft function in the absence of immunosuppression. This condition is associated with an expansion of CD4(+)CD25(+)FoxP3(+) T regulatory cells in the spleen. Unfortunately, stable graft function was accompanied by constant and reproducible development of NPC-derived cancer mainly sustained by insulin secretion.

Conclusion: These data demonstrate that the use of NPC in combination with islets prevents graft rejection in a fully mismatched model. However, the development of NPC-derived cancer raises serious doubts about the safety of using adult stem cells in combination with insulin-producing cells outside the original microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells
  • Animals
  • Diabetes Mellitus, Experimental / therapy*
  • Graft Rejection / prevention & control*
  • Islets of Langerhans
  • Islets of Langerhans Transplantation / adverse effects
  • Islets of Langerhans Transplantation / methods*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / etiology
  • Neoplasms / pathology
  • Neoplastic Stem Cells / pathology
  • Neurons
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Transplantation Tolerance*
  • Transplantation, Homologous