Stem cell
Mesenchymal Stem Cells Delivered at the Subcapsule of the Kidney Ameliorate Renal Disease in the Rat Remnant Kidney Model

https://doi.org/10.1016/j.transproceed.2009.01.072Get rights and content

Abstract

Stem cells (SC) are potential therapeutic tools in the treatment of chronic renal diseases. Number and engraftment of SC in the injured sites are important for possible differentiation into renal cells and paracrine effect. The aim of this study was to analyze the effect of subcapsular injection of mesenchymal stem cells (MSC) in the 5/6 nephrectomy model (5/6 Nx). MSC obtained from Wistar rats were isolated by their capacity to adhere to plastic surfaces, characterized by flow cytometry, and analyzed by their differentiation potential into osteoblasts. MSC (2 × 105) were injected into the subcapsule of the remnant kidney of male Wistar rats, and were followed for 15 or 30 days. 5/6 Nx rats showed significant hypertension at 15 and 30 days, which was reduced by MSC at 30 days. Increased albuminuria and serum creatinine at 15 and 30 days in 5/6 Nx rats were also reduced by subcapsular injection of MSC. We also observed a significant reduction of glomerulosclerosis index 30 days after injection of MSC. 4–6 diamidino-2-phenylindole dihydrochloride (DAPI)-stained MSC showed a migration of these cells into renal parenchyma 5, 15, and 30 days after subcapsular injection. In conclusion, our data demonstrated that subcapsular injection of MSC in 5/6 Nx rats is associated with renoprotective effects. These results suggest that locally implanted MSC in the kidney allow a large number of cells to migrate into the injured sites and demonstrate that subcapsular injection represent an effective route for MSC delivery.

Section snippets

MSC Isolation and Expansion

Briefly, bone marrow from femur and tibia of male Wistar rats (180–220 g, obtained from local colony) were flushed out and cultivated with Dulbecco's modified Eagle's medium–low glucose (DMEM-low) supplemented with 10% fetal bovine serum. MSC were isolated using their characteristic to adhere to plastic culture dishes. After 2 weeks of culture, adherent cells were harvested by trypsinization, washed with phosphate-buffered saline (PBS), and kept on ice until the moment of the infusion. For the

MSC Culture and Characterization

MSC isolated from femur and tibia bone marrow formed colonies of fibroblast-like cells after about 12–20 days of culture, and grew into a homogeneous population of cells, with a mainly fusiform morphology. Analysis of cell surface markers using flow cytometry showed that MSC were positive for CD44 (61 ± 8%) and CD90 (85 ± 4%), and mostly negative for CD31 (2.5 ± 0.5%), CD34 (4 ± 1%), and CD45 (19 ± 4%; Fig 1.).

Osteogenic Differentiation of MSC

After 3 weeks of culture in osteogenic induction medium, MSC acquired an

Discussion

In this study, we have shown that MSC isolated from rat bone marrow and injected into the subcapsule of remnant kidney rats with the 5/6 Nx experimental model of chronic progressive nephropathy significantly ameliorated renal function 30 days after nephrectomy, however, it was already detected at 15 days.

Although no unique surface marker can be used for specific characterization of MSC, these cells can be identified by combined expression of cell surface markers and exclusion of others. In our

Acknowledgments

The authors thank Laila Casado and Fernanda Cobucci for their skillful technical assistance and gratefully acknowledge Dr Denis Feliers for his excellent help in reviewing the manuscript.

References (13)

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Supported by CNPq (Brazilian Council for Scientific and Technologic Development) number 552644/2005-6 and by FAPESP (Foundation for Research Support) number 2006/56628-4.

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