Transplante de células-tronco mesenquimais de medula óssea em ratos com hipertensão renovascular

• Autor(a) principal: Lira, Rafaelle Cavalcante de
• Data de Publicação: 2017
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12673
• topic: Chronic kidney disease; Renovascular hypertension; Mesenchymal stem cell; Na++K+-ATPase; Doença renal crônica; Hipertensão renovascular; Célula-tronco mesenquimal; Na++K+-ATPase; Rins Doenças; Insuficiência renal crônica; Hipertensão renovascular; CNPQ::CIENCIAS BIOLOGICAS

Renovascular hypertension (RVH) results from a decrease in renal blood flow due to renal artery stenosis and the subsequent activation of the renin-angiotensin-aldosterone system (RAAS) is the starting point of systemic hypertension. RVH is a progressive disease that, leads to the establishment of chronic kidney disease (CKD), when untreated. There is no specific treatment available, and in advanced stages, the only alternative treatment is dialysis and/or renal transplantation. The lack of available organs for transplant, among other factors, limits this treatment and leads to the development of new functional therapies. Mesenchymal stem cells (MSCs) have become major candidates because its ability to preserve renal function and attenuate renal damage through the production of cytokines and growth factors (Van Koppen et al, 2012). In this work, we evaluated the therapeutic effects of bone marrow MCSs transplantation under renal subcapsular region, in renovascular hypertension experimental model (in left renal artery clipping, two kidneys, one clip 2K1C). The morphological and functional changes were analyzed, including the Na++K+-ATPase activity and expression, the expression of angiotensin converting enzyme (ACE) and angiotensin type 1 (AT1R) and type 2 (AT2R) receptors. Wistar rats (n = 18) were divided into 3 groups: Sham, 2K1C and 2K1C + MSC (received transplantation after 4 weeks of clipping). Euthanasia occurred after 2 weeks of transplantation (week 6), where the kidneys were collected and processed for microscopy and Western blotting. To MSC tracking in the renal parenchyma, we used GFP + cells at the transplant and the analysis was performed by flow cytometry and immunoperoxidase. 2K1C animals developed hypertension accompanied by increased expression of renin, ACE, AT1R and reduced activity and expression of Na++K+-ATPase and AT2R. CTM therapy decreased systolic blood pressure, renin expression, ACE, AT1R, and restored the activity and expression of Na++K+-ATPase and AT2R. In addition, MSC transplantation reduced fibrosis and TGF-β expression, contributing to the glomeruli and tubules remodeling. We also observed podocin expression increase, reduction in proteinuria, plasma urea and glucose levels, and plasma protein levels restoration. We conclude that a single MSC transplantation under subcapsular region in 2K1C model was able to promote beneficial effects on morphological and functional remodeling, making it an effective therapy for chronic kidney disease.