Centro Interdipartimentale di Biotecnologie Molecolari "Guido Tarone"
- Professor Emeritus Molecular Biotechnology Center “Guido Tarone”, University of Torino
- 1994-2022 Full Professor of Molecular Genetics, Department of Molecular Biotechnology and Health Sciences, University of Torino
- Valentina Fonsato
- Chiara Pasquino
- Veronica Dimuccio
- Giorgio Nicolò
- Sveva Cecchi
- Kevin Beltramolli
- Nicola Moser
- Lorenzo Silengo
Research activity
Research on murine starch on murine stem cells
During the last 2 decades, there has been a significant interest in exploring the developmental plasticity of pluripotent germ cells. Spermatogonial stem cells have been successfully isolated from both human and murine testis. These pluripotent stem cells, known as germ line cell-de- rived pluripotent stem cells (GPSCs) have been induced to differentiate into various cell types, including car- diomyocytes and neurons, among others. This exciting potential opens up new avenues for research and holds promise for future applications in regenerative medicine and tissue engineering.
Hepatic differentiation
We successfully generated hepatocytes from mouse GPSCs with high efficiency and thoroughly characterized their functionality. Moreover, we demonstrated that these differentiated cells have the capability to engraft within the mouse liver following partial hepatectomy. This exciting discovery opened up new possibilities for using GPSC-derived hepatocytes in potential regenerative therapies and liver-related research (PMID: 26323094).
Renal differentiation
We also showed that GPSCs can undergo differentia- tion, resulting in the development of functional renal tu- bular-like cells in vitro (GTCs). Through an in vivo model of kidney ischemia, our research showed that GTCs offer remarkable protection against both acute and chronic kidney damage. These findings hold significant promise for potential therapeutic applications in treating kid- ney-related conditions and promoting renal regeneration (PMID: 24136918).
Research on human stem cells - Therapy for human metabolic diseases
Crigler Najjar Syndrome type I (CNSI) is a rare recessive disorder caused by mutations in the Ugt1a1 gene. Unfortunately, there is currently no permanent cure for this condition, and liver transplantation remains the main treatment option despite its limitations. As an alternative approach, stem cell-based therapy holds promise for ad- dressing this disorder. To explore this potential, we con- ducted experiments using human liver stem cells (HLSC) in immune-compromised NOD SCID Gamma (NSG)/Ugt1-/- mice, which closely resemble the pathological manifestations found in CNSI patients.
We showed that the HLSC-injected mutant mice exhib- ited remarkable recovery from brain damage in comparison to the controls. These findings provide a compelling proof-of-concept, demonstrating that HLSC therapy can effectively treat CNSI in this animal model. These promising results pave the way for potential therapeutic applications of HLSC-based treatments in patients with CNSI (PMID: 31965023).
Cancer immunotherapy using chimeric antigen recep- tor (CAR) T cells is the first approved genetically modified cellular therapy and has become a standard treatment for many hematological malignancies showing great efficacy and safety.
However off-target toxicity has been observed mainly due to organ or tissue damage caused by massive inflammatory citokines release induced by the treatment.
To explore T cell location following the infusion of the modified cells imaging tools will be used in collaboration with the Eurobioimaging team of the MBC. These data could be very important to improve the success of the therapy and to avoid off-target toxicity.
Telethon 2017-2018 N° GGP14020 Terapia cellulare per la sindrome di Crigler-Najjar di tipo I con cellule staminali epatiche umane 312.400 euro
FESR 2021 Regione Piemonte: codice domanda 378-20-Sviluppo di test molecolari su campioni salivari per la diagnosi di SARS-Cov-2 € 508.384,00
POR FESR 2014/2020 - Bando Piattaforma tecnologica Salute e Benessere – progetto “Terapie avanzate per processi fibritici cronici (EVER)” € 3.527.891
Erasmus+, Key Action 2, 2019: Cooperation for in- novation and the exchange of good practices (Grant Agreement n. 2019-2146/001-001) Modernisation de la formation en Biotechnologie en Tunisie et devel- oppement de l’employabilite des diplomes 72.728,00 euro
National Project ALISEI: CTN01_00177_88744 460 IRMI: Italian Infrastructure for Regenerative Medicine 500.000 euro
2022WFXCWM PRIN 2022 pilot in vitro and in vivo study for molecular characterization of epidermal stem cells and quality and safety assessment of epidermal cultures for combined cell and gene therapy 324.000 euro
Fagoonee S, Arigoni M, Manco M, Olivero M, Bizzaro F, Magagnotti C, Andolfo A, Miniscalco B, Forni M, Todeschi S, Tolosano E, Bocchietto E, Calogero R, Altruda
F. Circulating Extracellular Vesicles Contain Liver-Derived RNA Species as Indicators of Severe Cholestasis-Induced Early Liver Fibrosis in Mice. Antioxid Redox Signal. 2022 Jan 4. doi: 10.1089/ars.2021.0023.
Petrillo S, Manco M, Altruda F, Fagoonee S, Tolosano E Liver Sinusoidal Endothelial Cells at the Crossroad of Iron Overload and Liver Fibrosis..Antioxid Redox Signal. 2021 Aug 20;35(6):474-486. doi: 10.1089/ ars.2020.8168. Epub 2020 Aug 27
Petrillo S, Carrà G, Bottino P, Zanotto E, De Santis MC, Margaria JP, Giorgio A, Mandili G, Martini M, Cavallo R, Barberio D, Altruda F A Novel Multiplex qRT-PCR Assay to Detect SARS-CoV-2 Infection: High Sensitivity and Increased Testing Capacity. .Microorganisms. 2020 Jul 17;8(7):1064. doi: 10.3390/microorganisms8071064.
Famulari ES, Navarro-Tableros V, Herrera Sanchez MB, Bortolussi G, Gai M, Conti L, Silengo L, Tolosano E, Tetta C, Muro AF, Camussi G, Fagoonee S, Altruda F. Human liver stem cells express UGT1A1 and improve phenotype of immunocompromised Crigler Najjar syndrome type I mice. Sci Rep. 2020 21;10(1):887. doi: 10.1038/s41598-020-57820-2.PMID: 31965023
De Chiara L, Famulari ES, Fagoonee S, van Daalen SKM, Buttiglieri S, Revelli A, Tolosano E, Silengo L, van Pelt AMM, Altruda F.Characterization of Human Mesenchymal Stem Cells Isolated from the Testis. Stem Cells Int. 2018; 2018:4910304. doi:10.1155/2018/4910304.
Fusella F, Seclì L, Busso E, Krepelova A, Moiso E, Rocca S, Conti L, Annaratone L, Rubinetto C, Mello-Grand M, Singh V, Chiorino G, Silengo L, Altruda F, Turco E, Morotti A, Oliviero S, Castellano I, Cavallo F, Provero P, Tarone G, Brancaccio The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis. Nat Commun. 2017 Nov 21;8(1):1636. doi: 10.1038/ s41467-017-01829-1.
Fagoonee S, Famulari ES, Silengo L, Camussi G, Altruda F. Prospects for Adult Stem Cells in the Treatment of Liver Diseases. Stem Cells Dev. 2016, 25(20):1471- 1482. doi: 10.1089/scd.2016.0144.
De Chiara L, Fagoonee S, Ranghino A, Bruno S, Camussi G, Tolosano E, Silengo L, Altruda F.J Renal cells from spermatogonial germline stem cells protect against kidney injury. Am Soc Nephrol. 2014 Feb;25(2):316-28. doi: 10.1681/ASN.2013040367.
Chiabrando D, Marro S, Mercurio S, Giorgi C, Petrillo S, Vinchi F, Fiorito V, Fagoonee S, Camporeale A, Turco E, Merlo GR, Silengo L, Altruda F, Pinton P, Tolosano
E. The mitochondrial heme exporter FLVCR1b mediates erythroid diferentiation. J Clin Invest. 2012 Dec;122(12):4569-79. doi: 10.1172/JCI62422.
Hobbs RM, Fagoonee S, Papa A, Webster K, Altruda F, Nishinakamura R, Chai L, Pandolf PP. Functional antagonism between Sall4 and Plzf defnes germline progenitors. Cell Stem Cell. 2012 Mar 2;10(3):284-98. doi: 10.1016/j.stem.2012.02.004.
