Noninvasive monitoring of immunosuppressive drug efficacy to prevent rejection of intracerebral glial precursor allografts

Michael Gorelik, Miroslaw Janowski, Chulani Galpoththawela, Robert Rifkin, Michael Levy, Barbara Lukomska, Douglas A. Kerr, Jeff W Bulte, Piotr Walczak

Research output: Contribution to journalArticle

Abstract

The development of cell-based therapies opens up new avenues for treating a myriad of diseases of the central nervous system (CNS). While significant effort is being directed toward development of patient-specific, autologous transplantable cells, at present, the majority of cell transplantation studies performed clinically utilize allografts. In this context, the issue of graft rejection and immunoprotection is of key importance. In this study, we transplanted mouse glial-restricted progenitors into immunodeficient, immunocompetent, and immunosuppressed mice and monitored their survival noninvasively using bioluminescence imaging (BLI). With the use of serial BLI, we evaluated both the prevalence and dynamics of cell rejection. We demonstrate that allografts in immunocompetent mice were rejected at a rate of 69.2% (n = 13) indicating that graft tolerance is possible even without immunosuppression. Immunosuppression using a combination of rapamycin and FK506 or cyclosporine failed to fully protect the grafts. FK506 and rapamycin treatment resulted in a slight improvement of immunoprotection (22.2% rejected, n = 9) compared to cyclosporin A (55.6% rejected, n = 9); however, the difference was not significant. Notably, immunohistochemistry revealed leukocytes infiltrating the graft area in both rejecting and nonrejecting immunocompetent animals, but not in immunodeficient animals. The induction of an inflammatory process, even in surviving allografts, has implications for their long-term survival and functionality.

Original languageEnglish (US)
Pages (from-to)2149-2157
Number of pages9
JournalCell Transplantation
Volume21
Issue number10
DOIs
StatePublished - 2012

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Drug Monitoring
Immunosuppressive Agents
Grafts
Neuroglia
Allografts
Tacrolimus
Sirolimus
Bioluminescence
Immunosuppression
Cyclosporine
Monitoring
Transplantation Tolerance
Transplants
Animals
Survival
Central Nervous System Diseases
Cell Transplantation
Graft Rejection
Cell- and Tissue-Based Therapy
Imaging techniques

Keywords

  • Allograft
  • Bioluminescence
  • Glial restricted precursors
  • Immunosuppression
  • Rejection
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Noninvasive monitoring of immunosuppressive drug efficacy to prevent rejection of intracerebral glial precursor allografts. / Gorelik, Michael; Janowski, Miroslaw; Galpoththawela, Chulani; Rifkin, Robert; Levy, Michael; Lukomska, Barbara; Kerr, Douglas A.; Bulte, Jeff W; Walczak, Piotr.

In: Cell Transplantation, Vol. 21, No. 10, 2012, p. 2149-2157.

Research output: Contribution to journalArticle

Gorelik, Michael ; Janowski, Miroslaw ; Galpoththawela, Chulani ; Rifkin, Robert ; Levy, Michael ; Lukomska, Barbara ; Kerr, Douglas A. ; Bulte, Jeff W ; Walczak, Piotr. / Noninvasive monitoring of immunosuppressive drug efficacy to prevent rejection of intracerebral glial precursor allografts. In: Cell Transplantation. 2012 ; Vol. 21, No. 10. pp. 2149-2157.
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