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Genetically engineered Sertoli cells are able to survive allogeneic transplantation

Gene Therapy volume 11, pages 694–700 (2004)Cite this article

Abstract

The immunoprotective nature of the testis has led to numerous investigations for its ability to protect cellular grafts. Sertoli cells (SCs) are at least partially responsible for this immunoprotective environment and survive allogeneic and xenogeneic transplantation. The ability of SCs to survive transplantation leads to the possibility that they could be engineered to deliver therapeutic proteins. As a model to test this hypothesis, we examined the ability of SCs that produce green fluorescent protein (GFP) to survive transplantation and continue expressing GFP. SCs were isolated from transgenic mice engineered to express GFP and transplanted as aggregates under the kidney capsule of severe combined immunodeficient (SCID) and Balb/c mice. Using this paradigm, it was possible to compare the survival of transgenic SCs directly in both immunodeficient and immunocompetent recipients. Fluorescence microscopy of the kidney capsule and immunohistochemistry of the grafts for GFP and GATA-4 revealed the presence of GFP-expressing SCs under the kidney capsule of SCID and Balb/c mice at both 30 and 60 days post-transplantation. In contrast, islets transplanted to Balb/c mice were rejected. Thus, SCs survive transplantation and continue to express GFP raising the possibility that SCs can be engineered using transgenic technology to produce proteins, such as insulin, factor VIII, or dopamine for the treatment of diabetes, hemophilia or Parkinson's disease, respectively.

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Acknowledgements

This work was funded by the Alberta Heritage Foundation for Medical Research (AHFMR), Canadian Diabetes Association (CDA), Canadian Institutes of Health Research, a collaborative grant from the Juvenile Diabetes Research Foundation International (JDRF) and Sertoli Technologies, Inc., Edmonton Civic Employees' Charitable Assistance Fund and MacLachlan Fund. GSK is a senior scholar of the AHFMR and recipient of a scholarship from the CDA and a Career Development Award from the JDRF. JMD is a recipient of a Postdoctoral Fellowship from the JDRF and the Izaak Walton Killiam Memorial. We acknowledge the technical assistance of Daniel Bruch, Deb Dixon, Lynnette Elder, Crystal Harris and Monique Tourand.

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Authors and Affiliations

  1. Department of Surgery, Surgical-Medical Research Institute, University of Alberta, Edmonton, T6G 2N8, Canada

    J M Dufour, G S Korbutt & R V Rajotte

  2. Department of General Surgery and The Transplant Center, Carolinas Medical Center, Charlotte, 28232, NC, USA

    R Hemendinger, C R Halberstadt & P Gores

  3. Sertoli Technologies, Inc, Cranston, 02921, RI, USA

    D F Emerich

  4. Department of Medicine, University of Alberta, Edmonton, T6G 2N8, Canada

    R V Rajotte

Authors
  1. J M Dufour
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  2. R Hemendinger
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  3. C R Halberstadt
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  4. P Gores
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  5. D F Emerich
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  6. G S Korbutt
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  7. R V Rajotte
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Dufour, J., Hemendinger, R., Halberstadt, C. et al. Genetically engineered Sertoli cells are able to survive allogeneic transplantation. Gene Ther 11, 694–700 (2004). https://doi.org/10.1038/sj.gt.3302218

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