Survival and distribution of injected haematopoietic stem cells in acute kidney injury.

BACKGROUND: Endogenous bone marrow-derived cells are known to incorporate into renal epithelium at a low rate. Haematopoietic stem cells (HSCs) rather than mesenchymal stem cells (MSC) are responsible for this phenomenon. MSCs have the potential to ameliorate kidney function after acute kidney injury (AKI) without directly repopulating the tubules. However, little is known about the short-term effect of HSCs. METHODS: In this article, we analysed the survival rate and organ distribution of isolated rat HSCs injected into the renal artery after ischaemic renal injury, using quantitative real-time PCR, as well as their impact on renal function and histomorphology. RESULTS: Intra-arterially injected Lin(-)CD90(+) HSCs were detected in the kidney at significant amounts only within the first 24 h after injection and were virtually absent by Day 2. Compared with control animals, no differences were seen after HSC administration with respect to kidney function or histomorphologic changes of AKI. At Day 7 HSCs were again readily detectable in the kidney suggesting a redistribution of cells at later time points. Of note, HSCs did not seem to have an exclusive tropism for the injured kidney but were detectable in the lungs, liver, spleen, heart and brain at all time points. CONCLUSIONS: Injected HSCs do not appear to significantly contribute to tubular repair or ameliorate renal damage in ischaemic AKI although they may show considerable engraftment in various organs. These data further challenge the concept that injection of HSCs may be used as a therapeutic approach in treating AKI.

Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury.

BACKGROUND: Although renal tubular epithelium has a great capacity for repair it has been suggested that the administration of mesenchymal stem cells may accelerate the recovery following severe ischemic injury. METHODS: Here we analyzed the survival rate and organ distribution of transplanted mesenchymal stem cells as well as their contribution to kidney regeneration after ischemic renal injury using functional tests, histological examination as well as quantitative real-time PCR. RESULTS: Intravenously injected stem cells were mainly trapped in lungs and liver. One hour after injection, less than 1% of the injected stem cells could be detected in the injured kidneys. These cells disappeared within the first few days and did not replace renal epithelial cells precluding substantial transdifferentiation. To clarify whether reinforced stem cell delivery might promote sustained survival or conversion to tubular epithelia, stem cells were directly injected into the injured kidneys. Although these grafted cells also did not show sustained survival or contribute to structural renal repair, stem cell injection was associated with a significant but transient initial decrease in serum creatinine. CONCLUSION: These data suggest that mesenchymal stem cells do not significantly contribute to epithelial renewal after ischemic injury, promoting the idea that the major impact of cell-based therapy for acute kidney injury may result from paracrine or endocrine effects unrelated to stem cell transdifferentiation.