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TISSUE-SPECIFIC STEM CELLS |
aThe Ira B. Black Center for Stem Cell Research and the Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA;
bM.D./Ph.D. Program, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, USA;
cThe Joint Graduate Program in Toxicology, Rutgers University, Piscataway, New Jersey, USA
Key Words. Mesenchymal stem cells • Bone marrow stromal cells • Cell transplantation • Mesenchymal stem cell transplantation • Graft rejection
Correspondence: Thomas M. Coyne, Ph.D., UMDNJ-RWJMS, SPH Bldg., Rm. 366, 683 Hoes Lane, Piscataway, New Jersey 08854-5635, USA. Telephone: 732-235-5387; Fax: 732-235-4990; e-mail: coynetm{at}umdnj.edu
Received March 23, 2006;
accepted for publication July 17, 2006.
First published online in STEM CELLS EXPRESS July 27, 2006.
ABSTRACT: The remarkable plasticity of marrow stromal cells (MSCs) after transplantation to models of neurological disease and injury has been described. In this report, we investigated the plasticity and long-term survival of MSCs transplanted into the normal brain. MSCs were isolated from green fluorescent protein (GFP) transgenic rats and double-labeled with 5-bromo-2-deoxyuridine (BrdU) and bis benzamide (BBZ) prior to transplantation into the adult hippocampus or striatum. Surgery elicited an immediate inflammatory response. MSC grafts were massively infiltrated by ED1-positive microglia/macrophages and surrounded by a marked astrogliosis. By 14 days, graft volume had retracted and GFP immunoreactivity was absent, indicating complete donor rejection. Consequently, MSCs did not exhibit plasticity formerly identified in other studies. However, BrdU- and BBZ-labeled cells were detected up to 12 weeks. Control transplants of nonviable MSCs demonstrated the transfer of donor labels to host cells. Unexpectedly, BrdU labeling was colocalized to host phagocytes, astrocytes, and neurons in both regions. Our results indicate that MSCs transplanted to the intact adult brain are rejected by an inflammatory response. Moreover, use of the traditional cell labels BrdU and BBZ may provide a misleading index of donor survival and differentiation after transplantation.
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