Application of Bone Marrow-Derived Stem Cells in Experimental Nephrology

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Abstract

Recent advancement in developmental biology has led to the discovery of immature mesenchymal stem cells in bone marrow and several established organs. The therapeutic potentials of such stem cells for treating serious diseases constitute a major rationale for every research effort, and clinical trials for replacing some damaged tissues such as cartilage are currently under way. Although the feasibility of such stem cell therapies for renal diseases remains unknown, it is worthy of pursuing possibilities. As an experimental tool, we have made chimeric rats that carry the bone marrow of transgenic rats expressing green fluorescent protein (GFP) throughout the body. All marrow lineages can be traced with bright green fluorescence regardless of their terminal phenotypes in chimeric rats. When compared with other conventional strategies for tracking bone marrow-derived cells, our system is highly sensitive and allows us to take advantage of the rat nephrology. Using this system, we have reported that bone marrow provides mesangial cells during repair process. In this manuscript, we briefly summarize our experiences.

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G Ferrari, Fulvio Mavilio (1998)

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Oligodendrocyte precursors survive poorly and do not migrate following transplantation into the normal adult central nervous system.

M T O'Leary, W F Blakemore (1997)

Cell cultures enriched for oligodendrocyte precursors were prepared for male neonatal rat pups and transplanted into the spinal cord white matter of normal and x-irradiated syngeneic adult female rats. Transplanted cells were detected using a probe specific for the rat Y chromosome immediately after transplantation and 14 days later. In non-x-irradiated tissue, significantly fewer cells were seen at 14 days compared with time zero, and no cell migration was observed. In x-irradiated tissue, cells both survived and migrated into the surrounding grey and white matter. The observed behaviour of oligodendrocyte precursors in normal adult tissue is in contrast to their behaviour in myelin mutants and neonates, where migration and survival have been well documented (Warrington et al., 1993; Lachapelle et al., 1994), but mimics the behaviour of the O-2A progenitor-like cell line, CG4, following transplantation into similar environments (Franklin et al., 1996). The findings in this study have profound implications for the use of grafts of oligodendrocyte precursors as a therapy in human demyelinating diseases, because they indicate that grafts will need to be introduced directly into each clinically relevant area of demyelination.