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Laboratory of
*
Vascular Biology and
Medical Biochemistry, The Picower Institute for Medical Research, Manhasset, NY 11030
Fibrocytes are a distinct population of blood-borne cells that
display a unique cell surface phenotype (collagen
I+/CD11b+/CD13+/CD34+/CD45RO+/MHC
class II+/CD86+) and exhibit potent
immunostimulatory activities. Circulating fibrocytes rapidly enter
sites of tissue injury, suggesting an important role for these cells in
wound repair. However, the regulatory processes that govern the
differentiation of blood-borne fibrocytes and the mechanisms that
underlie the migration of these cells to wound sites are currently not
known. We report herein that ex vivo cultured fibrocytes can
differentiate from a CD14+-enriched mononuclear cell
population and that this process requires contact with T cells.
Furthermore, we demonstrate that TGF-
1 (1–10 ng/ml), an important
fibrogenic and growth-regulating cytokine involved in wound healing,
increases the differentiation and functional activity of cultured
fibrocytes. Because fibrocytes home to sites of tissue injury, we
examined the role of chemokine/chemokine receptor interactions in
fibrocyte trafficking. We show that secondary lymphoid chemokine, a
ligand of the CCR7 chemokine receptor, acts as a potent stimulus for
fibrocyte chemotaxis in vitro and for the homing of injected fibrocytes
to sites of cutaneous tissue injury in vivo. Finally, we demonstrate
that differentiated, cultured fibrocytes express 
smooth muscle
actin and contract collagen gels in vitro, two characteristic features
of wound-healing myofibroblasts. These data provide important insight
into the control of fibrocyte differentiation and trafficking during
tissue repair and significantly expand their potential role during
wound healing.
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L. Zhang, N. J. Freedman, L. Brian, and K. Peppel Graft-Extrinsic Cells Predominate in Vein Graft Arterialization Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 470 - 476. [Abstract] [Full Text]
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Y. Li, W. Foster, B. M. Deasy, Y. Chan, V. Prisk, Y. Tang, J. Cummins, and J. Huard Transforming Growth Factor-{beta}1 Induces the Differentiation of Myogenic Cells into Fibrotic Cells in Injured Skeletal Muscle: A Key Event in Muscle Fibrogenesis Am. J. Pathol., March 1, 2004; 164(3): 1007 - 1019. [Abstract] [Full Text] [PDF]
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H. Robertson, S. Ali, B. J. McDonnell, A. D. Burt, and J. A. Kirby Chronic Renal Allograft Dysfunction: The Role of T Cell-Mediated Tubular Epithelial to Mesenchymal Cell Transition J. Am. Soc. Nephrol., February 1, 2004; 15(2): 390 - 397. [Abstract] [Full Text] [PDF]
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M. Niku, L. Ilmonen, T. Pessa-Morikawa, and A. Iivanainen Limited Contribution of Circulating Cells to the Development and Maintenance of Nonhematopoietic Bovine Tissues Stem Cells, January 1, 2004; 22(1): 12 - 20. [Abstract] [Full Text] [PDF]
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 T. Schuler, S. Kornig, and T. Blankenstein Tumor Rejection by Modulation of Tumor Stromal Fibroblasts J. Exp. Med., November 17, 2003; 198(10): 1487 - 1493. [Abstract] [Full Text] [PDF]
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D. Pilling, C. D. Buckley, M. Salmon, and R. H. Gomer Inhibition of Fibrocyte Differentiation by Serum Amyloid P J. Immunol., November 15, 2003; 171(10): 5537 - 5546. [Abstract] [Full Text] [PDF]
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N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al. Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105. [Full Text] [PDF]
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N. C. Direkze, S. J. Forbes, M. Brittan, T. Hunt, R. Jeffery, S. L. Preston, R. Poulsom, K. Hodivala-Dilke, M. R. Alison, and N. A. Wright Multiple Organ Engraftment by Bone-Marrow-Derived Myofibroblasts and Fibroblasts in Bone-Marrow-Transplanted Mice Stem Cells, September 1, 2003; 21(5): 514 - 520. [Abstract] [Full Text] [PDF]
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M. Schmidt, G. Sun, M. A. Stacey, L. Mori, and S. Mattoli Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma J. Immunol., July 1, 2003; 171(1): 380 - 389. [Abstract] [Full Text] [PDF]
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 T. P. Amadeu, B. Coulomb, A. Desmouliere, and A. M. A. Costa Cutaneous Wound Healing: Myofibroblastic Differentiation and in Vitro Models International Journal of Lower Extremity Wounds, June 1, 2003; 2(2): 60 - 68. [Abstract] [PDF]
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 M. Kimatrai, C. Oliver, A. C. Abadia-Molina, J. M. Garcia-Pacheco, and E. G. Olivares Contractile Activity of Human Decidual Stromal Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 844 - 849. [Abstract] [Full Text] [PDF]
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H Nakayama, H Enzan, E Miyazaki, and M Toi {alpha} Smooth muscle actin positive stromal cells in gastric carcinoma J. Clin. Pathol., October 1, 2002; 55(10): 741 - 744. [Abstract] [Full Text] [PDF]
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Y. Li and J. Huard Differentiation of Muscle-Derived Cells into Myofibroblasts in Injured Skeletal Muscle Am. J. Pathol., September 1, 2002; 161(3): 895 - 907. [Abstract] [Full Text] [PDF]
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M Brittan, T Hunt, R Jeffery, R Poulsom, S J Forbes, K Hodivala-Dilke, J Goldman, M R Alison, and N A Wright Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon Gut, June 1, 2002; 50(6): 752 - 757. [Abstract] [Full Text] [PDF]
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N. Scholler, M. Hayden-Ledbetter, A. Dahlin, I. Hellstrom, K. E. Hellstrom, and J. A. Ledbetter Cutting Edge: CD83 Regulates the Development of Cellular Immunity J. Immunol., March 15, 2002; 168(6): 2599 - 2602. [Abstract] [Full Text] [PDF]
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 I. HARTLAPP, R. ABE, R. W. SAEED, T. PENG, W. VOELTER, R. BUCALA, and C. N. METZ Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo FASEB J, October 1, 2001; 15(12): 2215 - 2224. [Abstract] [Full Text] [PDF]
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