In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal
ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to
immunomodulation. To this end, Wistar rats (200-250 g) were submitted to 1-hour
ischemia and treated with NPCs (4 x 10(6) cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with
carboxyfluorescein diacetate succinimydylester (
CFSE). Kidneys were harvested for analysis of
cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum
creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78 mg/dl, p < 0.05) and acute tubular
necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-
CFSE and
glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker)
mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-beta and
TNF-alpha expression and higher anti-inflammatory
IL-4 and
IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory
cytokines (IL-1beta, TNF-alpha and INF-gamma). Our data suggested that NPC
therapy improved renal function by influencing immunological responses.