Are stem cell characteristics altered by disease state?
Autologous stem cell transplantation combined with gene therapy can potentially be used to treat genetically inherited diseases. However, characterization of multipotential cells from a disease state remains extremely limited. We have characterized adult bone marrow stromal cells (MSCs) derived from three retinal degenerative mouse models and compared them to marrow stromal cells derived from their normal strain counterparts. Despite similar profiles soon after harvest, at 30 days postisolation, marrow stromal cells derived from a disease origin were shown to contain a large pool (approximately 89-99%) of undifferentiated marrow stromal cells (CD90(+)/STRO-1(+)) as compared to their normal counterparts (approximately 19-43%). Fetal bovine serum appeared essential for marrow stromal cell proliferation and was not found to induce differentiation, although it could be substituted with other additives including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and leukemia inhibitory factor (LIF). We also showed that resulting CD90(+)/STRO(+) cells derived from both states could be directed into desired lineages expressing at the same rate and that they could be transduced with the same efficiency using different viral vehicles. This investigation has shown the existence of a large pool of undifferentiated stem cells derived from the disease state that have the potential to form the desired cell types when appropriately cued.
Kicic
Anthony
A
Stem Cell Unit, Department of Molecular Ophthalmology, Lions Eye Institute and the University of Western Australia, Nedlands, 6009, Western Australia, Australia. anthonyk@ichr.uwa.edu.au
Hall
Christine M
CM
Shen
Wei-Yong
WY
Rakoczy
P Elizabeth
PE
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014161:Transduction, Genetic