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Published on: July 2, 2020
Mesenchymal Stromal Cells Induce Podocyte Protection in the Puromycin Injury Model
Felipe Mateus Ornellas1, Rodrigo J Ramalho2, Camilla Fanelli2
1Laboratory of Cellular and Molecular Physiology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Podocytes are specialized cells with a limited capacity for cell division that do not regenerate in response to injury and loss. Insults that compromise the integrity of podocytes promote proteinuria and progressive renal disease. The aim of this study was to evaluate the potential renoprotective and regenerative effects of mesenchymal stromal cells (mSC) in a severe form of the podocyte injury model induced by intraperitoneal administration of puromycin, aggravated by unilateral nephrectomy. Bone derived mSC were isolated and characterized according to flow cytometry analyses and to their capacity to differentiate into mesenchymal lineages. Wistar rats were divided into three groups: Control, PAN, and PAN+ mSC, consisting of PAN rats treated with 2 × 105 mSC. PAN rats developed heavy proteinuria, hypertension, glomerulosclerosis and significant effacement of the foot process. After 60 days, PAN rats treated with mSC presented a significant amelioration of all these abnormalities. In addition, mSC treatment recovered WT1 expression, improved nephrin, podocin, synaptopodin, podocalyxin, and VEGF expression, and downregulated proinflammatory Th1 cytokines in the kidney with a shift towards regulatory Th2 cytokines. In conclusion, mSC administration induced protection of podocytes in this experimental PAN model, providing new perspectives for the treatment of renal diseases associated with podocyte damage.
Insights
Mesenchymal stromal cells (mSC) protected podocytes from puromycin-induced injury in rats. This cell therapy ameliorated kidney damage and improved protein expression, offering new hope for treating podocyte diseases.
Area of Science:
- Nephrology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Podocytes are crucial for kidney filtration and have limited regenerative capacity.
- Podocyte injury leads to proteinuria and progressive renal disease.
- Developing treatments to protect or regenerate podocytes is essential.
Purpose of the Study:
- To investigate the renoprotective and regenerative potential of mesenchymal stromal cells (mSC) in a severe podocyte injury model.
- To evaluate mSC effects on proteinuria, hypertension, and glomerulosclerosis.
- To assess mSC impact on key podocyte markers and inflammatory profiles.
Main Methods:
- Bone-derived mSC were isolated and characterized.
- A severe podocyte injury model was induced in Wistar rats using puromycin and unilateral nephrectomy (PAN model).
- PAN rats were treated with mSC (2 × 10^5 cells) and compared to control and PAN-only groups over 60 days.
Main Results:
- mSC treatment significantly ameliorated proteinuria, hypertension, and glomerulosclerosis in PAN rats.
- mSC administration restored expression of WT1, nephrin, podocin, synaptopodin, podocalyxin, and VEGF.
- mSC therapy shifted the renal cytokine profile from pro-inflammatory Th1 to regulatory Th2.
Conclusions:
- Mesenchymal stromal cells demonstrate significant renoprotective effects in a severe experimental podocyte injury model.
- mSC treatment promotes podocyte integrity and function, suggesting therapeutic potential.
- This study opens new avenues for treating renal diseases linked to podocyte damage.
