Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia.
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.
Coyne
Thomas M
TM
The Ira B. Black Center for Stem Cell Rersearch and Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA. coynetm@umdnj.edu
Marcus
Akiva J
AJ
Woodbury
Dale
D
Black
Ira B
IB
D000818:Animals; D030801:Animals, Genetically Modified; D016477:Artifacts; D001549:Benzamides / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006084:Graft Rejection; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics; D013194:Staining and Labeling / Q000379:methods; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation
D001549:Benzamides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine