Journal article

Short-term inhibition of p53 combined with keratinocyte growth factor improves thymic epithelial cell recovery and enhances T-cell reconstitution after murine bone marrow transplantation

Ryan M Kelly, Emily M Goren, Patricia A Taylor, Scott N Mueller, Heather E Stefanski, Mark J Osborn, Hamish S Scott, Elena A Komarova, Andrei V Gudkov, Georg A Hollaender, Bruce R Blazar

BLOOD | AMER SOC HEMATOLOGY | Published : 2010

Abstract

Myeloablative conditioning before bone marrow transplantation (BMT) results in thymic epithelial cell (TEC) injury, T-cell immune deficiency, and susceptibility to opportunistic infections. Conditioning regimen-induced TEC damage directly contributes to slow thymopoietic recovery after BMT. Keratinocyte growth factor (KGF) is a TEC mitogen that stimulates proliferation and, when given before conditioning, reduces TEC injury. Some TEC subsets are refractory to KGF and functional T-cell responses are not fully restored in KGF-treated BM transplant recipients. Therefore, we investigated whether the addition of a pharmacologic inhibitor, PFT-beta, to transiently inhibit p53 during radiotherapy c..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


Awarded by Swiss National Science Foundation (SNF)


Awarded by National Center for Research Resources (NCRR) Shared Instrumentation


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

We thank Drs Philippe Bouillet and Andreas Strasser for providing Bim<SUP>-/-</SUP> mice, Dr Sing Sing Way (University of Minnesota) for providing Lm-OVA, Drs Chris Contag and Jonathan Hardy (Stanford University) for providing Lm- 2C, and Ann Bohac (Oligonucleotide & Peptide Synthesis Facility, BioMedical Genomics Center, University of Minnesota) for help with primer design and for rapid and reliable primer synthesis. We also thank Steven Highfill for critical reading of the manuscript.This work was supported by the National Institutes of Health (grants R01-HL073794, R01-HL55209, R01-A1057477-01, R01A1057477-01, R01-CA75179, P01CA067493), Swiss National Science Foundation (SNF; grant 3100-68310.02), the Children's Cancer Research Fund (CCRF), and a grant from the European Community 6th Framework Program Eurothymaid Integrated Project. We acknowledge the use of the confocal microscope made available through a National Center for Research Resources (NCRR) Shared Instrumentation Grant (no. 1 S10 RR16851).