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Title: Effect of foetal and adult stem cells in acute and chronic kidney diseases
Author: Rota , Cinzia
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2012
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Acute kidney injury (AKl) and chronic kidney disease (CKD) are serious illnesses associated to high mortality and unsatisfactory therapeutic treatments. In search for new therapies, it has become evident that stem cells could be a possible option for patients with AKI and CKD. The evidence of the reno protective effect of bone marrow-mesenchymal stem cells (BM-MSCs) in experimental model of AKl, prompted us to study the effect of stem cells isolated from sources that are more accessible as cord blood (CB) and amniotic fluid. Infusion of hCB-MSCs in inununodeficient mice with AKI ameliorated renal function and tubular structure, prolonging survival. Moreover, transplanted hCB-MSCs localized in peritubular areas, limiting oxidative stress and apoptosis. By virtue of stem cell capacity to produce growth factors, hCB-MSCs were able- to induce the pro-survival factor Akt in tubular cells and subsequently their proliferation. Using the well-established model of AKI in immunodeficient mice, we studied the pro-regenerative effect of amniotic fluid stem (hAFS) cells. Infusion of hAPS cells in cisplatin-mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. These cells engrafted injured kidney predominantly in peri tubular region and through a paracrine mechanism are able to exert an anti-apoptotic effect, to activate AId and stimulate proliferation of tubular cells. We enhanced the therapeutic potential of hAFS cells by cell pretreatment with GDNF, which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartnent. In AKI models, the renoprotective effect of BM-MSCs is well established, however the role of these stem cells in model of eKD is controversial and not demonstrated so far. Therefore, we tested the effect of BM-MSCs in a model of adriarnycin-induced nephropathy. Repeated infusions of BMMSCs limited podocyte loss, and normalized distribution of parietal epithelial cells along the Bowman's capsule, reducing glomerulosclerosis. Moreover, through the local release of growth factors as VEGF, BM-MSCs were able to provide a local pro-survival environment that limited glomerular inflanunation and microvascular rarefaction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available