Mesenchymal Stem Cell-Mediated Delivery of the Sodium Iodide Symporter Supports Radionuclide Imaging and Treatment of Breast Cancer

被引:83
作者
Dwyer, Roisin M. [1 ,4 ]
Ryan, James
Havelin, Ronan J. [5 ]
Morris, John C. [6 ]
Miller, Brian W. [7 ,8 ]
Liu, Zhonglin [7 ,8 ]
Flavin, Richard [3 ]
O'Flatharta, Cathal [4 ]
Foley, Mark J. [5 ]
Barrett, Harrison H. [7 ,8 ]
Murphy, J. Mary [4 ]
Barry, Frank P. [4 ]
O'Brien, Timothy [2 ,4 ]
Kerin, Michael J.
机构
[1] Natl Univ Ireland Galway, Div Surg, Sch Med, Discipline Surg, Galway, Ireland
[2] Natl Univ Ireland Galway, Discipline Med, Sch Med, Galway, Ireland
[3] Natl Univ Ireland Galway, Discipline Pathol, Sch Med, Galway, Ireland
[4] Natl Univ Ireland Galway, Regenerat Med Inst, Galway, Ireland
[5] Natl Univ Ireland Galway, Sch Phys, Galway, Ireland
[6] Mayo Clin, Div Endocrinol, Rochester, MN USA
[7] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA
[8] Univ Arizona, Ctr Gamma Ray Imaging, Tucson, AZ 85724 USA
基金
爱尔兰科学基金会;
关键词
Sodium iodide symporter; Mesenchymal stem cell; Breast cancer; Gene therapy; In vivo imaging; Radiotherapy; IN-VIVO; STROMAL CELLS; BONE-MARROW; TARGETED-DELIVERY; ADIPOSE-TISSUE; TUMOR STROMA; EXPRESSION; THERAPY; DIFFERENTIATION; VEHICLES;
D O I
10.1002/stem.665
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by (99m)Technetium pertechnetate imaging 3-14 days later using a BazookaSPECT gamma-camera. Tissue was harvested for analysis of human NIS (hNIS) expression by relative quantitative-polymerase chain reaction. Therapy animals received an i.p. injection of I-131 or saline 14 days after injection of MSC-NIS, and tumor volume was monitored for 8 weeks. After injection of MSC-NIS, BazookaSPECT imaging revealed an image of animal intestines and chest area at day 3, along with a visible weak tumor image. By day 14, the tumor was visible with a significant reduction in radionuclide accumulation in nontarget tissue observed. hNIS gene expression was detected in the intestines, heart, lungs, and tumors at early time points but later depleted in nontarget tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of I-131 14 days after MSC-NIS injection. This resulted in a significant reduction in tumor growth (mean +/- SEM, 236 +/- 62 mm(3) vs. 665 +/- 204 mm(3) in controls). The ability to track MSC migration and transgene expression noninvasively in real time before therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer. STEM CELLS 2011;29:1149-1157
引用
收藏
页码:1149 / 1157
页数:9
相关论文
共 49 条
[1]
[Anonymous], J CLIN ENDOCRINOL ME
[2]
Mesenchymal stem cells: clinical applications and biological characterization [J].
Barry, FP ;
Murphy, JM .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2004, 36 (04) :568-584
[3]
VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma [J].
Beckermann, B. M. ;
Kallifatidis, G. ;
Groth, A. ;
Frommhold, D. ;
Apel, A. ;
Mattern, J. ;
Salnikov, A. V. ;
Moldenhauer, G. ;
Wagner, W. ;
Diehlmann, A. ;
Saffrich, R. ;
Schubert, M. ;
Ho, A. D. ;
Giese, N. ;
Buechler, M. W. ;
Friess, H. ;
Buechler, P. ;
Herr, I. .
BRITISH JOURNAL OF CANCER, 2008, 99 (04) :622-631
[4]
Bone Marrow Multipotent Mesenchymal Stroma Cells Act as Pericyte-like Migratory Vehicles in Experimental Gliomas [J].
Bexell, Daniel ;
Gunnarsson, Salina ;
Tormin, Ariane ;
Darabi, Anna ;
Gisselsson, David ;
Roybon, Laurent ;
Scheding, Stefan ;
Bengzon, Johan .
MOLECULAR THERAPY, 2009, 17 (01) :183-190
[5]
Bieback K, 2008, BIO-MED MATER ENG, V18, pS71
[6]
Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate [J].
DiGirolamo, CM ;
Stokes, D ;
Colter, D ;
Phinney, DG ;
Class, R ;
Prockop, DJ .
BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (02) :275-281
[7]
Genetically targeted radiotherapy for multiple myeloma [J].
Dingli, D ;
Diaz, RM ;
Bergert, ER ;
O'Connor, MK ;
Morris, JC ;
Russell, SJ .
BLOOD, 2003, 102 (02) :489-496
[8]
Predominant intracellular overexpression of the Na+/I- symporter (NIS) in a large sampling of thyroid cancer cases [J].
Dohán, O ;
Baloch, Z ;
Bánrévi, Z ;
Livolsi, V ;
Carrasco, N .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (06) :2697-2700
[9]
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].
Dominici, M. ;
Le Blanc, K. ;
Mueller, I. ;
Slaper-Cortenbach, I. ;
Marini, F. C. ;
Krause, D. S. ;
Deans, R. J. ;
Keating, A. ;
Prockop, D. J. ;
Horwitz, E. M. .
CYTOTHERAPY, 2006, 8 (04) :315-317
[10]
Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells [J].
Dwyer, R. M. ;
Potter-Beirne, S. M. ;
Harrington, K. A. ;
Lowery, A. J. ;
Hennessy, E. ;
Murphy, J. M. ;
Barry, F. P. ;
O'Brien, T. ;
Kerin, M. J. .
CLINICAL CANCER RESEARCH, 2007, 13 (17) :5020-5027