Diverse Sources of Stem Cells to Treat Acute Kidney Injury

precursor cells (NPCs) can be protective in a rat ischemic AKI model. Fetal rat telencephalon-derived neurospheres were administered intravenously (i.v.), intraperitoneally (i.p.), and intracortically 4 h following 1 h of kidney ischemia. Control cells were homogenates from adult rat cerebellum. Intravenous administration of the neural precursor cells was highly effective in reducing the kidney dysfunction and structural damage at 24 h, and some benefit was seen from i.p. and intracortical administration as well. Labeled NPCs tracked to injured kidney, and there were enhanced levels of anti-inflammatory cytokines IL-4 and IL-10, while reduced levels of proinflammatory cytokines IL-1 and TNF in the kidney. Furthermore, macrophage infiltration was reduced after NPC administration. The authors are likely the first to demonstrate that NPCs are effective in AKI, which is an important conceptual advance in the field of stem cells and kidney diseases. A strength is that the design is clinically geared, studying various forms of administration. The injured kidney is providing homing signals that attract these progenitor cells, though what these are is unknown. The reduced macrophage trafficking and alterations in soluble inflammatory molecules are suggestive of an immune/anti-inflammatory mechanism of action, however reduced injury through other mechanisms may have led to this inflammatory profile. These fascinating results raise many questions. What are these NPCs making and could glial-derived neurotropic factor (GDNF) be one of these protective factors, as already demonstrated with GDNF administration [6, 7] ? Can other areas of the brain Ischemic acute kidney injury (AKI) decreases allograft survival in kidney transplants and increases mortality when occurring in native kidneys [1] . There is currently no specific treatment, thus there is an important need to develop novel ways to decrease early injury and augment repair. There is great promise in the application of stem cells for AKI, and the mechanisms by which stem cells work are largely unknown [2, 3] . Putative mechanisms of stem cell action have included transdifferentiation, fusion of stem cells into damaged tissue, immunomodulation, production of paracrine growth factors, or a combination of these mechanisms. Furthermore, it was once believed that stem cells originating from a particular tissue would support and construct tissue of similar type only. Recent studies challenge the notion of linear and unidirectional differentiation of lineage-committed adult stem cells. New lines of evidence invoke transdifferentiation to a wider spectrum of differentiated progeny than previously claimed [4, 5] . Undifferentiated or already differentiated cells or tissue-specific stem cells have been shown to alter their phenotype to express functional characteristics of a different tissue. These types of conversions are referred to as transdifferentiation or metaplasia and are accompanied by change in tissue-specific cell surface markers and phenotype. Another novel approach is to harness paracrine factors produced by stem cells and apply them to injured tissue to simulate stem cell repair function. In the current issue of Nephron, Wang et al. [pp e20– e28] from Brazil have elegantly demonstrated that neural Published online: April 3, 2009