Implications of microvesicles in therapeutic pathway of mesenchymal stem cells and their protective role against ischaemia reperfusion induced kidney injury / Heba Adel Abdelghaffar ; Supervised Mervat Elansary , Reem Jan Farid , Engy Elkhateeb

Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Background: Several studies demonstrated that mesenchymal stem cells (MSCs) reverse acute kidney injury (AKI) by a paracrine mechanism rather than by MSCs differentiation. Extracellular vesicles (EVs) released from MSCs may account for this paracrine mechanism by a horizontal transfer of messenger RNA and microRNA.Methods: EVs isolated from hWJUC-MSCs by ultracentrifugation, characterized by electron microscopy & flow cytometry. EVs were injected intravenously in rats immediately after monolateral left renal artery and vein occlusion for 45 min. To evaluate the EVs effects on AKI& induced by ischaemia{u2013} reperfusion injury (IRI) at day 2 and the progression to chronic kidney disease (CKD) at day 14, the animals were divided into different groups: normal rats (n = 5), IRI rats at day 2(n = 5), IRI + EVs rats at day 2 (n = 5), and IRI rats at day 14(n = 5), IRI+ EVs rats at day 14(n = 5), and all animals were sacrificed at day 2, day 14 respectively after the operation. Results: We found that a single administration of EVs, immediately after IRI, protects rats from AKI by inhibiting apoptosis and stimulating tubular epithelial cell proliferation. The EVs also significantly reduced the impairment of renal functions. Moreover, EVs by reducing the acute injury also protected from later progression to chronic kidney disease.Conclusion: EVs released from MSCs could be exploited as a new3cell free3 therapeutic approach for regenerative medicine. A single administration of hWJMSC-EVs immediately after IRI could ameliorate kidney ischemia/reperfusion injury both in the acute stage and prevent progression to chronic stages.

Issued also as CD