Neural Stem Cells-Cancer-Neurodegenerative DiseasePrincipal Investigator: John S. Yu, MD
Funded by an NIH grant, the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center is focused on novel cellular therapies for brain tumors and other neurological disorders using neural stem cells. Stem cells appear to be integral in the cause and formation of brain tumors, and Institute research has demonstrated that neural stem cells may be used in the treatment of neurological disorders. The Institute's laboratory is placing a major emphasis on the development of neural stem cells from bone marrow to treat brain tumors and neurodegenerative disorders. Neural stem cells have the ability to track tumor cells and areas of neurodegeneration. This property will be exploited in order to use neural stem cells as delivery vehicles for tumoricidal or neuroprotective agents.
Brain Tumor Focus
Recent observations have demonstrated that cancer stem cells are chemoresistant and may be the major reason for the recurrence of these deadly tumors. These are the sole cells of the tumor that can initiate and propagate the tumor. Efficacy and safety studies are underway to develop vaccines that target the cancer stem cell. The goal of this work is to hit cancer at its root. By immunologically targeting cancer stem cells, the barrier of resistance of these cells to radiation and chemotherapy may be overcome.
Bringing Research to Clinical Trials
The laboratory is also actively developing a clinical protocol using neural stem cells derived from bone marrow to treat patients with brain tumors and neurodegenerative diseases such as Parkinson's disease and amyotropich lateral sclerosis (ALS).
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Xu Q, Yuan X, Liu G, Black KL, Yu JS. Hedgehog signaling regulates brain tumor stem cell self-renewal and portends a shorter survival for patients with PTEN-coexpressing glioblastomas. Stem Cells, DOI:10.1634/stemcells.2008-0459 (Advance Online Version).
Ghods AJ, Irvin D, Liu G, Yuan X, Abdulkadir IR, Tunici P, Konda B, Wachsmann Hogiu S, Black KL, Yu JS. Spheres Isolated from 9L Gliosarcoma Rat Cell Line Possess Chemoresistant and Aggressive Cancer Stem-Like Cells. Stem Cells 2007 2:1645-53.
Yu JJ, Sun X, Yuan X, Lee JW, Snyder EY, Yu JS. Immunomodulatory neural stem cells for brain tumor therapy. Exp Op Biol Ther 2006 Dec 6 (12):1255-1262.
Zeng Z, Liu G, Yuan X, Zeng Xianhao, Zeng Xiaorong, Ng H, Chen H, Jiang T, Akasaki Y, Kessey K, Black KL, Yu JS. Manipulation of proliferation and differentiation of human bone marrow derived neural stem cells in vitro and in vivo. J of Neurosci Res 2007 Feb 1;85(2):310-20.
Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 2006 Dec 2;5:67.
Hu J, Yuan X, Belladonna ML, Ong JM, Wachsmann-Hogiu S, Farkas DL, Black KL, Yu JS. Induction of potent antitumor immunity by intratumoral injection of interleukin 23-transduced dendritic cells. Cancer Res. 2006 Sep 1; 66(17): 8887-96.
Yuan X, Hu J, Belladonna M, Black KL, Yu JS. IL-23 expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma. Cancer Res 2006 Mar 1; 66(5):2630-8.
Liu G, Akasaki Y, Khong HT, Wheeler CJ, Das A, Black KL, Yu JS. Cytotoxic T cell targeting of TRP-2 Sensitizes human malignant glioma to chemotherapy. Oncogene 2005 Aug 4; 24(33):5226-5234.
Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS, Isolation of cancer stem Cells from adult glioblastoma multiforme. Oncogene 2004 Dec16; 23(58):9392-400.
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