title: A clinically relevant in vivo zebrafish model of human multiple myeloma to study preclinical therapeutic efficacy.
abstract: Patient-derived multiple myeloma (MM) cells are difficult to establish in culture or propagate in vivo in murine model. Here, we describe a zebrafish xenograft model that permits rapid, reliable growth of human MM cells injected into the perivitelline space of albino zebrafish (Casper) embryos 48 hours postfertilization. MM1S and MM1R MM cell lines and primary CD138(+) MM cells were stained with CM-Dil red fluorescent dye and suspended in Matrigel prior to their injection. The cells grew at the site of injection and disseminated throughout the developing embryos and larvae. Tumor size was quantified by fluorescent microscopy, and cell fate was followed for 4 days. All of the cell line xenografts showed responses similar to those previously observed with in vitro assays. CD138(+) plasma cell xenografts derived from MM patients also grew and were inhibited by the same drugs patients had responded to clinically. Using this technique, we can assess drug sensitivity or resistance with a small number of MM cells in a short period. This raises the possibility that one might be able to assess drug sensitivity in real time with readily obtainable clinical samples.
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Jianhong
authors.initials: J
authors.lastname: Lin
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA; Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, People's Republic of China;
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Medical Oncology, and.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zhao
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Ariel H
authors.initials: AH
authors.lastname: Kwart
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA; Department of Clinical Laboratory, The 4th Hospital of Haerbin Medical University, Heilongjiang, China;
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Biotherapy Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, People's Republic of China;
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Handin
authors.affiliation: Medical Oncology, and LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA; VA Boston Healthcare System, Boston, MA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D015027:Zebrafish / Q000378:metabolism*