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Title: Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia.

Authors: Coyne, Thomas M; Marcus, Akiva J; Woodbury, Dale; Black, Ira B

Published In Stem Cells, (2006 Nov)

Abstract: 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.

PubMed ID: 16873764 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Genetically Modified; Artifacts*; Benzamides/metabolism; Bone Marrow Cells/metabolism; Bone Marrow Cells/pathology*; Bone Marrow Transplantation*; Brain/metabolism; Brain/pathology*; Brain/surgery; Bromodeoxyuridine/metabolism; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Female; Graft Rejection*; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Inflammation/metabolism; Inflammation/pathology*; Male; Mesenchymal Stem Cell Transplantation*; Neuroglia/metabolism; Neuroglia/pathology; Neurons/metabolism; Neurons/pathology; Rats; Rats, Sprague-Dawley/genetics; Staining and Labeling/methods; Stromal Cells/metabolism; Stromal Cells/pathology*; Stromal Cells/transplantation

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