Dottorato in Fisiopatologia Medica

Contatti

Supervisore

Maria Felice Brizzi

Attività di ricerca

Project

Regenerative potential of stem cell derived extracellular vesicles in Kidney disease

Background

Kidney interstitial fibrosis is one of the characteristic features and underlying cause of all forms of chronic kidney disease progression and development. In pathological conditions, injured cells release cytokines and chemokines as well as inflammatory molecules which lead to the homing of immune cells such as monocytes, macrophages, dendritic cells etc to the site of injury. Activation of the immune system also triggers the wound healing system primarily characterised by fibroblast activation and differentiation to myofibroblasts. Other cells such as pericytes, and tubular epithelial cells have also been reported to undergo epithelial to mesenchymal transition (EMT) allowing them to exhibit fibroblast like characteristics and function. Dysregulation of this mechanism leads to the deposition of pathological matrix comprising primarily of proteins such as fibronectin, collagen 1, 3 and 4 in the kidney parenchyma amplifying the injury and accelerating nephron demise. Tissue growth factor beta 1 (TGF-β1), through the mothers against decapentaplegic (SMAD) pathway is considered as one of the main regulators of fibrosis and EMT in various pathological conditions including renal fibrosis. Therefore, targeting the process of fibrogenesis primarily through the inhibition of regulators such as TGF-β1 and fibroblasts could prove beneficial in slowing the progression of chronic kidney disease.

Stem cell derived EVs like their cells of origin have been reported to mimic the paracrine actions and therefore contribute towards various therapeutic benefits observed by the cells including renal protection and regeneration. The aim of this study is therefore to investigate whether EVs from HLSCs contribute towards tubular regeneration and alleviate fibrosis in-vitro and in-vivo.

 

Articles Published (Selected articles)

Kholia S, Paper, Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells--possible role in SLE. Biochem Biophys Res Commun. 2010 Jul.

Kholia S, Paper, A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma. J Immunol Methods. 2011 Aug.

Kholia S, Paper, A novel role for peptidylarginine deiminases in microvesicle release reveals therapeutic potential of PAD inhibition in sensitizing prostate cancer cells to chemotherapy. J Extracell Vesicles. 2015 Jun

Kholia S, Review, Stem Cell-Derived Extracellular Vesicles and Immune-Modulation, Front Cell Dev Biol. 2016 Aug.

Kholia S, Paper, Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells. , Tissue Eng Part A. 2017 Nov;23(21-22):1262-1273.

Kholia S, Paper, Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency. Stem Cell Res Ther. 2017 Jul 27

Kholia S, Paper, Human Liver Stem Cell-Derived Extracellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis. Front Immunol. 2018 Jul 19

Kholia S, Paper, Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis , Int J Cancer. 2018 Aug 15.

 

Congresses Attended

• ISEV2018 Barcelona - Poster presentation: Human Liver stem cell derived EVs abrogate fibrotic markers in TGF-β1 activated Fibroblasts 

 

Attended Lectures

• Riccarda Granata - Come scrivere e pubblicare un lavoro scientifico - 12 Jun 2018
• Luigi Biancone - Trapianto di rene apettiimmunologici e attualita e prospettive della terapia immunosoppressiva - 27 Jul 2018

 

• Course in RICERCHE BIBLIOGRAFICHE Group 2 - 25 and 28 May - 8 hours total
• D-Day - 13/09/2018: Talk 1: The spare part: Reflection of Kidney transplantation - Prof. Andrea Pietrabissa
• D-Day - 13/09/2018: Talk 2:Reprogramming of metabolic pathways by PI3 kinase and AKT signalling in cancer - Prof. Alex Toker