Abstract
Objectives The aim of this study was to evaluate the effects of bone marrow stromal stem cells (BMSCs) on renal ischemia-reperfusion injury (RIRI) and dynamically monitor engrafted BMSCs in vivo for the early prediction of their therapeutic effects in a rat model. Methods A rat model of RIRI was prepared by clamping the left renal artery for 45 min. One week after renal artery clamping, 2 × 106 superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected into the renal artery. Next, MR imaging of the kidneys was performed on days 1, 7, 14, and 21 after cell transplantation. On day 21, after transplantation, serum creatinine (Scr) and urea nitrogen (BUN) levels were assessed, and HE staining and TUNEL assay were also performed. Results The body weight growth rates in the SPIO-BMSC group were significantly higher than those in the PBS group (P < 0.05), and the Scr and BUN levels were also significantly lower than those in the PBS group (P < 0.05). HE staining showed that the degree of degeneration and vacuole-like changes in the renal tubular epithelial cells in the SPIO-BMSC group was significantly better than that observed in the PBS group. The TUNEL assay showed that the number of apoptotic renal tubular epithelial cells in the SPIO-BMSC group was significantly lower than that in the PBS group. The T2 value of the renal lesion was the highest on day 1 after cell transplantation, and it gradually decreased with time in both the PBS and SPIO-BMSC groups but was always the lowest in the SPIO-BMSC group. Conclusion SPIO-labeled BMSC transplantation can significantly promote the recovery of RIRI and noninvasive dynamic monitoring of engrafted cells and can also be performed simultaneously with MRI in vivo for the early prediction of therapeutic effects.
Highlights
Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal failure (ARF), which has an increasing incidence and high mortality rates
After 7 days of culturing, the isolated bone marrow stromal stem cells (BMSCs) grew in clusters, displaying various sizes and spindle shapes, along with many hemocytes scattered amongst them (Figure 1(a))
The cell surface phenotype of the isolated BMSCs from passage 3 was analyzed by flow cytometry, with the results showing that the surface markers of the cells were positive for CD44 (99.80%), CD90 (97.44%), CD73 (99.78%), and CD105 (95.41%) and negative for CD34, CD45, CD11b, CD19, and HLA-DR, consistent with the expression of BMSCs surface markers (Figures 1(e)–1(i))
Summary
Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal failure (ARF), which has an increasing incidence and high mortality rates. It affects early functional recovery and the survival time of transplanted kidneys [1, 2]. Transplantation of bone marrow stromal stem cells (BMSCs) for the treatment of RIRI is a common research focus, owing to the excellent properties these cells possess, including ease of harvesting, low immunogenicity, multiple differentiation potential, and a decreased number of ethical issues in comparison to the use of other stem cell types. Of particular interest is the fact that BMSCs can differentiate into renal tubular epithelial cells, glomerular cells, and other kidney cells [3]. To investigate the therapeutic effects of BMSCs for RIRI, we administered BMSCs into a rat RIRI model via the renal artery
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