Stem Cells Derived from Human Amniotic Fluid Contribute to Acute Kidney Injury Recovery

Stem cells isolated from human amniotic fluid are gaining attention with regard to their therapeutic potential. In this work, we investigated whether these cells contribute to tubular regeneration after experimental acute kidney injury. Cells expressing stem cell markers with multidifferentiative potential were isolated from human amniotic fluid. The regenerative potential of human amniotic fluid stem cells was compared with that of bone marrow-derived human mesenchymal stem cells. We found that the intravenous injection of 3.5 × 10⁵ human amniotic fluid stem cells into nonimmune-competent mice with glycerol-induced acute kidney injury was followed by rapid normalization of renal function compared with injection of mesenchymal stem cells. Both stem cell types showed enhanced tubular cell proliferation and reduced apoptosis. Mesenchymal stem cells were more efficient in inducing proliferation than amniotic fluid-derived stem cells, which, in contrast, were more antiapoptotic. Both cell types were found to accumulate within the peritubular capillaries and the interstitium, but amniotic fluid stem cells were more persistent than mesenchymal stem cells. In vitro experiments demonstrated that the two cell types produced different cytokines and growth factors, suggesting that a combination of different mediators is involved in their biological actions. These results suggest that the amniotic fluid-derived stem cells may improve renal regeneration in acute kidney injury, but they are not more effective than mesenchymal stem cells.Stem cell-based therapy is a promising and plausible option for organ repair.¹ Several groups have been successful in demonstrating the use of different stem cell types in the treatment of acute kidney injury (AKI) in different experimental animal models. Ex vivo expanded mesenchymal stem cells (MSCs) or resident renal stem cells were used in these studies.¹ The advantage of MSC use in therapy is their pluripotency, the relative ease of isolation, and the possible ex vivo expansion of the cells.^2–5 It has been shown that MSCs may improve the recovery from cytotoxic^6,7 and ischemic AKI.^8,9 However, the exact mechanisms that promote kidney regeneration after stem cell injection are mostly unknown. The process might involve recruitment of stem cells to the site of injury, fusion of stem cells with injured cells, or most likely paracrine/endocrine stimulation.¹⁰ In addition, the best source of stem cells for therapeutic use remains to be defined.A number of studies focused on alternative sources of stem cells with multipotential differentiating capabilities and accessibility.^11–13 Mesenchymal stem cells obtained from the adipose tissue, the umbilical cord vein, and the dental pulp have been investigated as a potential source for stem cells to be used in tissue regeneration.^14–17 In search for alternative sources of stem cells, several groups have reported the isolation of stem cells from human amniotic fluids (hAFSCs) and their subsequent differentiation into all three types of germ layer cells.^18–22 Amniotic fluid (AF) supplies the developing embryo with nutrients and provides mechanical protection. AF contains cells of embryonic origin, and it is indeed used in routine prenatal diagnosis to test for chromosomal aberrations of the embryo.Perin et al²³ injected hAFSCs into murine embryonic kidneys and tested their contribution to the early renal development. They found that hAFSCs differentiated into renal vesicles and comma- and s-shaped bodies.Because the retrieval of hAFSCs is considered ethically acceptable and does not involve the destruction of human embryos, stem cells from amniotic fluid present an attractive alternative to embryonic stem cells.^24–27 A further finding that is making stem cells from AF a very attractive source for therapeutic use is the absence of teratoma formation when these cells are injected in vivo.²³The aim of the present study was to investigate whether hAFSCs may contribute to tubular regeneration in AKI induced by glycerol injection in non-immune-competent SCID mice. In addition, we aimed to compare the regenerative potential of hAFSCs with that of human bone marrow-derived MSCs.