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A Novel Clinical Grade Isolation Method for Human Kidney Perivascular Stromal Cells
Published on: August 7, 2017
Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and
Elizabeth B Oliveira-Sales1, Edgar Maquigussa, Patricia Semedo
1Departament of Medicine, Renal Division, Federal University of Sao Paulo, Sao Paulo, Brazil.
Abstract:
Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.
Insights
Mesenchymal stem cell therapy shows promise for renovascular hypertension. MSCs reduced blood pressure, proteinuria, and kidney damage in a rat model, offering a potential new treatment strategy.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Regenerative Medicine
Background:
- Renovascular hypertension (RVH) is a renin-angiotensin-system (RAS)-dependent condition characterized by renal vascular rarefaction and failure.
- RAS inhibitors are often ineffective in managing arterial pressure and preserving renal function in RVH.
- Novel therapeutic strategies are crucial for treating RVH and its associated renal complications.
Purpose of the Study:
- To investigate the efficacy of mesenchymal stem cell (MSC) therapy in a 2 Kidney-1 Clip (2K-1C) rat model of renovascular hypertension.
- To evaluate the impact of MSCs on arterial pressure, renal function, proteinuria, sympathetic activity, and intrarenal RAS expression.
Main Methods:
- Fluorescently tagged MSCs were administered weekly to 2K-1C hypertensive rats.
- Flow cytometry was used to track MSC distribution in the kidney.
- Arterial pressure, proteinuria, renal function, and sympathetic hyperactivity were assessed.
- Renal morphology, fibrosis, and vascular rarefaction were evaluated.
- Expression levels of key RAS components and inflammatory cytokines were measured.
Main Results:
- MSCs prevented further increases in arterial pressure and significantly reduced proteinuria and sympathetic hyperactivity.
- Treatment improved renal morphology, decreased fibrosis, and ameliorated renal vascular rarefaction.
- MSC therapy normalized the expression of intrarenal renin-angiotensin-system components (angiotensinogen, ACE, AT1 receptor) and inflammatory cytokines (IL-1β, TNF-α).
- MSCs were detected in the central nervous system, indicating potential blood-brain barrier crossing.
Conclusions:
- MSC therapy represents a promising strategy for treating renovascular hypertension and its renal consequences.
- The treatment effectively mitigates key pathological features of RVH, including elevated blood pressure, renal damage, and fibrosis.
- The observed normalization of the intrarenal RAS and reduction in inflammation contribute to the therapeutic benefits of MSCs.
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