Direct Orthotopic Transplantation of Fresh Surgical Specimen Preserves CD133+ Tumor Cells in Clinically Relevant Mouse Models of Medulloblastoma and Glioma (original) (raw)
Journal Article
Qin Shu ,
Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
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Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center
, Houston, Texas,
USA
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Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
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Department of Pathology, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
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Laboratory of Molecular Neuro-Oncology, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Search for other works by this author on:
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center
, Houston, Texas,
USA
Search for other works by this author on:
Department of Pathology, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Search for other works by this author on:
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
Search for other works by this author on:
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
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Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine
, Houston, Texas,
USA
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Received:
29 November 2007
Cite
Qin Shu, Kwong Kwok Wong, Jack M. Su, Adekunle M. Adesina, Li Tian Yu, Yvonne T. M. Tsang, Barbara C. Antalffy, Patricia Baxter, Laszlo Perlaky, Jianhua Yang, Robert C. Dauser, Murali Chintagumpala, Susan M. Blaney, Ching C. Lau, Xiao-Nan Li, Direct Orthotopic Transplantation of Fresh Surgical Specimen Preserves CD133+ Tumor Cells in Clinically Relevant Mouse Models of Medulloblastoma and Glioma, Stem Cells, Volume 26, Issue 6, June 2008, Pages 1414–1424, https://doi.org/10.1634/stemcells.2007-1009
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Abstract
Recent identification of cancer stem cells in medulloblastoma (MB) and high-grade glioma has stimulated an urgent need for animal models that will not only replicate the biology of these tumors, but also preserve their cancer stem cell pool. We hypothesize that direct injection of fresh surgical specimen of MB and high-grade glioma tissues into anatomically equivalent locations in immune-deficient mouse brains will facilitate the formation of clinically accurate xenograft tumors by allowing brain tumor stem cells, together with their non-stem tumor and stromal cells, to grow in a microenvironment that is the closest to human brains. Eight of the 14 MBs (57.1%) and two of the three high-grade gliomas (66.7%) in this study developed transplantable (up to 12 passages) xenografts in mouse cerebellum and cerebrum, respectively. These xenografts are patient specific, replicating the histopathologic, immunophenotypic, invasive/metastatic, and major genetic (analyzed with 10K single nucleotide polymorphism array) abnormalities of the original tumors. The xenograft tumor cells have also been successfully cryopreserved for long-term preservation of tumorigenicity, ensuring a sustained supply of the animal models. More importantly, the CD133+ tumor cells, ranging from 0.2%–10.4%, were preserved in all the xenograft models following repeated orthotopic subtransplantations in vivo. The isolated CD133+ tumor cells formed neurospheres and displayed multi-lineage differentiation capabilities in vitro. In summary, our study demonstrates that direct orthotopic transplantation of fresh primary tumor cells is a powerful approach in developing novel clinical relevant animal models that can reliably preserve CD133+ tumor cell pools even during serial in vivo subtransplantations.
Disclosure of potential conflicts of interest is found at the end of this article.
Copyright © 2008 AlphaMed Press
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