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1. Impairment of Renal and Hematopoietic Stem/Progenitor Cell Compartments in Frailty Syndrome: Link with Oxidative Stress, Plasma Cytokine Profiles and Nuclear DNA Damage

Author

Bombelli, S, Grasselli, C, Mazzola, P, Veronesi, V, Morabito, I, Zucchini, N, Scollo, C, Blanco, S, De Marco, S, Torsello, B, Vitarelli, F, Antolini, L, Bianchi, C, Leoni, V, Bellelli, G, Perego, R, Bombelli, Silvia, Grasselli, Chiara, Mazzola, Paolo, Veronesi, Valentina, Morabito, Ivana, Zucchini, Nicola, Scollo, Chiara M, Blanco, Salvatore I, De Marco, Sofia, Torsello, Barbara, Vitarelli, Federica, Antolini, Laura, Bianchi, Cristina, Leoni, Valerio, Bellelli, Giuseppe, Perego, Roberto A, Bombelli, S, Grasselli, C, Mazzola, P, Veronesi, V, Morabito, I, Zucchini, N, Scollo, C, Blanco, S, De Marco, S, Torsello, B, Vitarelli, F, Antolini, L, Bianchi, C, Leoni, V, Bellelli, G, Perego, R, Bombelli, Silvia, Grasselli, Chiara, Mazzola, Paolo, Veronesi, Valentina, Morabito, Ivana, Zucchini, Nicola, Scollo, Chiara M, Blanco, Salvatore I, De Marco, Sofia, Torsello, Barbara, Vitarelli, Federica, Antolini, Laura, Bianchi, Cristina, Leoni, Valerio, Bellelli, Giuseppe, and Perego, Roberto A

Abstract

Frailty is an age-related syndrome that drives multiple physiological system impairments in some older adults, and its pathophysiological mechanisms remain unclear. We evaluated whether frailty-related biological processes could impair stem cell compartments, specifically the renal stem compartment, given that kidney dysfunctions are frequent in frailty. A well-characterized in vitro nephrosphere model of human adult renal stem/progenitor cells has been instrumental to and was appropriate for verifying this hypothesis in our current research. Evaluating the effects of plasma from older individuals with frailty (frail plasma) on allogeneic renal stem/progenitor cells, we showed significant functional impairment and nuclear DNA damage in the treated cells of the renal stem compartment. The analysis of the frail plasma revealed mitochondrial functional impairment associated with the activation of oxidative stress and a unique inflammatory mediator profile in frail individuals. In addition, the plasma of frail subjects also contained the highest percentage of DNA-damaged autologous circulating hematopoietic progenitor/stem cells. The integration of both molecular and functional data obtained allowed us to discern patterns associated with frailty status, irrespective of the comorbidities present in the frail individuals. The data obtained converged toward biological conditions that in frailty caused renal and hematopoietic impairment of stem cells, highlighting the possibility of concomitant exhaustion of several stem compartments.

Published
2024

2. Biological conditions related to friality and their effects on adult renal stem cells cultured as nephrospheres

Author

Grasselli, C, Bombelli, S, Tropeano, C, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Leoni, V, Bellelli, G, Perego, R, Grasselli C, Bombelli S, Tropeano C, De Marco S, Torsello B, Bianchi C, Antolini L, Mazzola P, Leoni V, Bellelli G, Perego RA, Grasselli, C, Bombelli, S, Tropeano, C, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Leoni, V, Bellelli, G, Perego, R, Grasselli C, Bombelli S, Tropeano C, De Marco S, Torsello B, Bianchi C, Antolini L, Mazzola P, Leoni V, Bellelli G, and Perego RA

Published
2022

3. DNA damage and reactive oxygen species as promising biological indicators of friality

Author

Bombelli, S, Grasselli, C, Tropeano, C, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Leoni, V, Bellelli, G, Perego, R, Bombelli S, Grasselli C, Tropeano C, De Marco S, Torsello B, Bianchi C, Antolini L, Mazzola P, Leoni V, Bellelli G, Perego RA, Bombelli, S, Grasselli, C, Tropeano, C, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Leoni, V, Bellelli, G, Perego, R, Bombelli S, Grasselli C, Tropeano C, De Marco S, Torsello B, Bianchi C, Antolini L, Mazzola P, Leoni V, Bellelli G, and Perego RA

Published
2022

4. High glucose induces an activated state of partial epithelial-mesenchymal transition in human primary tubular cell cultures

Author

Torsello, B, De Marco, S, Bombelli, S, Cifola, I, Morabito, I, Invernizzi, L, Meregalli, C, Zucchini, N, Strada, G, Perego, R, Bianchi, C, Torsello, Barbara, De Marco, Sofia, Bombelli, Silvia, Cifola, Ingrid, Morabito, Ivana, Invernizzi, Lara, Meregalli, Chiara, Zucchini, Nicola, Strada, Guido, Perego, Roberto A, Bianchi, Cristina, Torsello, B, De Marco, S, Bombelli, S, Cifola, I, Morabito, I, Invernizzi, L, Meregalli, C, Zucchini, N, Strada, G, Perego, R, Bianchi, C, Torsello, Barbara, De Marco, Sofia, Bombelli, Silvia, Cifola, Ingrid, Morabito, Ivana, Invernizzi, Lara, Meregalli, Chiara, Zucchini, Nicola, Strada, Guido, Perego, Roberto A, and Bianchi, Cristina

Abstract

Tubulointerstitial fibrosis is observed in diabetic nephropathy. It is still debated whether tubular cells, undergoing epithelial-mesenchymal transition (EMT) in high glucose (HG) conditions, may contribute to interstitial fibrosis development. In this study, we investigated the phenotypic and molecular EMT-like changes and the alteration of inflammatory and fibrogenic secretome induced by HG in human primary tubular cell cultures. Taking advantage of this in vitro cell model composed of proximal and distal tubular cells, we showed that HG-treated tubular cells acquired a fibroblast-like morphology with increased cytoplasmic stress fibers, maintaining the expression of the epithelial markers specific of proximal and distal tubular cells. HG increased Snail1, miRNA210 and Vimentin mesenchymal markers, decreased N-cadherin expression and migration ability of primary tubular cells, while E-cadherin expression and focal adhesion distribution were not affected. Furthermore, HG treatment of tubular cells altered the inflammatory cytokine secretion creating a secretome able to enhance the proliferation and migration of fibroblasts. Our findings show that HG promotes an activated state of partial EMT in human tubular primary cells and induces a pro-inflammatory and pro-fibrogenic microenvironment, supporting the active role of tubular cells in diabetic nephropathy onset.

Published
2023

6. Molecular characterization of nephrosphere-derived PKH/CD133+/CD24- stem-like cells evidenced possible new marker for renal stem cells in situ identification

Author

Bombelli, S, Eriani, S, Grasselli, C, Bolognesi, M, Rossetti, G, Ranzani, V, Torsello, B, De Marco, S, Bianchi, C, Pagani, M, Cattoretti, G, Perego, R, Bombelli S, Eriani S, Grasselli C, Bolognesi M, Rossetti G, Ranzani V, Torsello B, De Marco S, Bianchi C, Pagani M, Cattoretti G, Perego RA, Bombelli, S, Eriani, S, Grasselli, C, Bolognesi, M, Rossetti, G, Ranzani, V, Torsello, B, De Marco, S, Bianchi, C, Pagani, M, Cattoretti, G, Perego, R, Bombelli S, Eriani S, Grasselli C, Bolognesi M, Rossetti G, Ranzani V, Torsello B, De Marco S, Bianchi C, Pagani M, Cattoretti G, and Perego RA

Published
2021

7. Clear cell renal cell carcinoma invasion is modulated by TGFb/Arg interaction

Author

De Marco, S, Torsello, B, Bombelli, S, Grasselli, C, Zucchini, N, Strada, G, Perego, R, Bianchi, C, De Marco S, Torsello B, Bombelli S, Grasselli C, Zucchini N, Strada G, Perego RA, Bianchi C, De Marco, S, Torsello, B, Bombelli, S, Grasselli, C, Zucchini, N, Strada, G, Perego, R, Bianchi, C, De Marco S, Torsello B, Bombelli S, Grasselli C, Zucchini N, Strada G, Perego RA, and Bianchi C

Published
2021

8. PKHhigh/CD133+/CD24- Renal Stem-Like Cells Isolated from Human Nephrospheres Exhibit In Vitro Multipotency

Author

Bombelli, S, Meregalli, C, Grasselli, C, Bolognesi, M, Bruno, A, Eriani, S, Torsello, B, De Marco, S, Bernasconi, D, Zucchini, N, Mazzola, P, Bianchi, C, Grasso, M, Albini, A, Cattoretti, G, Perego, R, Bombelli S., Meregalli C., Grasselli C., Bolognesi M. M., Bruno A., Eriani S., Torsello B., De Marco S., Bernasconi D. P., Zucchini N., Mazzola P., Bianchi C., Grasso M., Albini A., Cattoretti G., Perego R. A., Bombelli, S, Meregalli, C, Grasselli, C, Bolognesi, M, Bruno, A, Eriani, S, Torsello, B, De Marco, S, Bernasconi, D, Zucchini, N, Mazzola, P, Bianchi, C, Grasso, M, Albini, A, Cattoretti, G, Perego, R, Bombelli S., Meregalli C., Grasselli C., Bolognesi M. M., Bruno A., Eriani S., Torsello B., De Marco S., Bernasconi D. P., Zucchini N., Mazzola P., Bianchi C., Grasso M., Albini A., Cattoretti G., and Perego R. A.

Abstract

The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKHhigh/CD133+/CD24- cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres generated spheroids with endothelial-like sprouts in Matrigel. We also demonstrated the double commitment toward endothelial and epithelial lineages of single RSC. The ability of the plastic RSC population to recapitulate the development of tubular epithelial and endothelial renal lineages makes these cells a good tool for the creation of organoids with translational relevance for studying the parenchymal and endothelial cell interactions and developing new therapeutic strategies.

Published
2020

9. Biological conditions related to frailty influence the behavior of renal stem/progenitor cells grown as nephrospheres

Author

Bombelli, S, Grasselli, C, Veronesi, V, Tropeano, C, Dominici, G, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Bellelli, G, Leoni, V, Perego, R, S. Bombelli, C. Grasselli, V. Veronesi, C. Tropeano, G. Dominici, S. De Marco, B. Torsello, C. Bianchi, L. Antolini, P. Mazzola, G. Bellelli, V. Leoni, R. A. Perego, Bombelli, S, Grasselli, C, Veronesi, V, Tropeano, C, Dominici, G, De Marco, S, Torsello, B, Bianchi, C, Antolini, L, Mazzola, P, Bellelli, G, Leoni, V, Perego, R, S. Bombelli, C. Grasselli, V. Veronesi, C. Tropeano, G. Dominici, S. De Marco, B. Torsello, C. Bianchi, L. Antolini, P. Mazzola, G. Bellelli, V. Leoni, and R. A. Perego

Published
2022

10. PPAR-alpha and PPAR-gamma involvement in grade-dependent lipid storage of clear cell renal cell carcinoma cells

Author

De Marco, S, Torsello, B, Morabito, I, Grasselli, C, Bombelli, S, Cifola, I, Zucchini, N, Perego, R, Bianchi, C, S. De Marco, B. Torsello, I. Morabito, C. Grasselli, S. Bombelli, I. Cifola, N. Zucchini, R. A. Perego, C. Bianchi, De Marco, S, Torsello, B, Morabito, I, Grasselli, C, Bombelli, S, Cifola, I, Zucchini, N, Perego, R, Bianchi, C, S. De Marco, B. Torsello, I. Morabito, C. Grasselli, S. Bombelli, I. Cifola, N. Zucchini, R. A. Perego, and C. Bianchi

Published
2022

12. Abl2 knockdown affects TGFb-mediated 3D invasion of ccRCC cells

Author

DE MARCO, S, Torsello, B, Minutiello, E, Bossi, M, Bombelli, S, Grasselli, C, Bianchi, C, Perego, R, De Marco Sofia, Torsello Barbara, Minutiello Emanuela, Bossi Mario, Bombelli Silvia, Grasselli Chiara, Bianchi Cristina, Perego Roberto, DE MARCO, S, Torsello, B, Minutiello, E, Bossi, M, Bombelli, S, Grasselli, C, Bianchi, C, Perego, R, De Marco Sofia, Torsello Barbara, Minutiello Emanuela, Bossi Mario, Bombelli Silvia, Grasselli Chiara, Bianchi Cristina, and Perego Roberto

Published
2021

13. Abl2 is required for TGFb1-induced invasion of clear cell Renal Cell Carcinoma cells

Author

Torsello, B, DE MARCO, S, Bossi, M, Bombelli, S, Grasselli, C, Zucchini, N, Bianchi, C, Perego, R, Torsello Barbara, De Marco Sofia, Bossi Mario, Bombelli Silvia, Grasselli Chiara, Zucchini Nicola, Bianchi Cristina, Perego Roberto, Torsello, B, DE MARCO, S, Bossi, M, Bombelli, S, Grasselli, C, Zucchini, N, Bianchi, C, Perego, R, Torsello Barbara, De Marco Sofia, Bossi Mario, Bombelli Silvia, Grasselli Chiara, Zucchini Nicola, Bianchi Cristina, and Perego Roberto

Published
2021

14. Abl2 is involved in TGF-induced invasion and invadopodia maturation of clear cell renal cell carcinoma cells

Author

De Marco, S, Torsello, B, Bombelli, S, Grasselli, C, Zucchini, N, Lucarelli, G, Perego, R, Bianchi, C, S. De Marco, B. Torsello, S. Bombelli, C. Grasselli, N. Zucchini, G. Lucarelli, R. Perego, C. Bianchi, De Marco, S, Torsello, B, Bombelli, S, Grasselli, C, Zucchini, N, Lucarelli, G, Perego, R, Bianchi, C, S. De Marco, B. Torsello, S. Bombelli, C. Grasselli, N. Zucchini, G. Lucarelli, R. Perego, and C. Bianchi

Published
2021

15. Abstracts of the 30th Meeting of the European Renal Cell Study Group (ERCSG)

Author

De Marco, S, Bianchi, C, Torsello, B, Bombelli, S, Zucchini, N, Viganò, P, Perego, R, De Marco S., Bianchi C., Torsello B., Bombelli S., Zucchini N., Viganò P., Perego R., De Marco, S, Bianchi, C, Torsello, B, Bombelli, S, Zucchini, N, Viganò, P, Perego, R, De Marco S., Bianchi C., Torsello B., Bombelli S., Zucchini N., Viganò P., and Perego R.

Published
2018

16. The dual role of Arg tyrosine kinase in tubulointerstitial fibrosis

Author

Torsello, B, DE MARCO, S, Bombelli, S, Cassina, V, Chisci, E, Bianchi, C, Perego, R, Torsello B., DE MARCO, SOFIA, Bombelli S., Cassina V., Chisci E., Bianchi C., Perego R., Torsello, B, DE MARCO, S, Bombelli, S, Cassina, V, Chisci, E, Bianchi, C, Perego, R, Torsello B., DE MARCO, SOFIA, Bombelli S., Cassina V., Chisci E., Bianchi C., and Perego R.

Published
2018

17. 36-kDa Annexin A3 Isoform Negatively Modulates Lipid Storage in Clear Cell Renal Cell Carcinoma Cells

Author

Bombelli, S, Torsello, B, De Marco, S, Lucarelli, G, Cifola, I, Grasselli, C, Strada, G, Bovo, G, Perego, R, Bianchi, C, Bombelli, Silvia, Torsello, Barbara, De Marco, Sofia, Lucarelli, Giuseppe, Cifola, Ingrid, Grasselli, Chiara, Strada, Guido, Bovo, Giorgio, Perego, Roberto, Bianchi, Cristina, Bombelli, S, Torsello, B, De Marco, S, Lucarelli, G, Cifola, I, Grasselli, C, Strada, G, Bovo, G, Perego, R, Bianchi, C, Bombelli, Silvia, Torsello, Barbara, De Marco, Sofia, Lucarelli, Giuseppe, Cifola, Ingrid, Grasselli, Chiara, Strada, Guido, Bovo, Giorgio, Perego, Roberto, and Bianchi, Cristina

Abstract

The adipocyte-like morphology of clear cell renal cell carcinoma (ccRCC) cells results from a grade-dependent neutral lipid accumulation; however, the molecular mechanism and role in renal cancer progression have yet to be clarified. ccRCC shows a gene expression signature consistent with adipogenesis, and the phospholipid-binding protein annexin A3 (AnxA3), a negative regulator of adipocyte differentiation, is down-regulated in RCC and shows a differential expression pattern for two isoforms of 36 and 33 kDa. Using primary cell cultures and cell lines, we investigated the involvement of AnxA3 isoforms in lipid storage modulation of ccRCC cells. We found that the increased accumulation of lipids into ccRCC cells correlated with a decrease of the 36/33 isoform ratio. Treatment with adipogenic medium induced a significant increment of lipid storage in ccRCC cells that had a low 36-kDa AnxA3 expression and 36/33 ratio. The 36-kDa AnxA3 silencing in ccRCC cells increased lipid storage induced by adipogenic medium. These data suggest that 36-kDa AnxA3 negatively modulates the response to adipogenic treatment and may act as negative regulator of lipid storage in ccRCC cells. The subcellular distribution of AnxA3 in the cellular endocytic compartment suggests its involvement in modulation of vesicular trafficking, and it might serve as a putative mechanism of lipid storage regulation in ccRCC cells, opening novel translational outcomes.

Published
2020

20. Role of interactions among Arg tyrosine kinase, TGFb1 and lysyl oxidase in ccRCC progression

Author

De Marco, S, Bianchi, C, Torsello, B, Meregalli, C, Bombelli, S, Zucchini, N, Viganò, P, STRADA, GUIDO RAFFAELE, Perego, R, De Marco, S, Bianchi, C, Torsello, B, Meregalli, C, Bombelli, S, Zucchini, N, Viganò, P, Strada, G, and Perego, R

Subjects
lysyl oxidase, Arg tyrosine kinase, TGFb1, clear cell Renal Cell Carcinoma, tumor progression
Published
2018

22. The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently

Author

Torsello, B, DE MARCO, S, Bombelli, S, Chisci, E, Cassina, V, Corti, R, Bernasconi, D, Giovannoni, R, Bianchi, C, Perego, R, DE MARCO, SOFIA, CHISCI, ELISA, CORTI, ROBERTA, Torsello, B, DE MARCO, S, Bombelli, S, Chisci, E, Cassina, V, Corti, R, Bernasconi, D, Giovannoni, R, Bianchi, C, Perego, R, DE MARCO, SOFIA, CHISCI, ELISA, and CORTI, ROBERTA

Abstract

The fibrotic tissue and the stroma adjacent to cancer cells are characterised by the presence of activated fibroblasts (myofibroblasts) which play a role in creating a supportive tissue charac-terised by abundant extracellular matrix (ECM) secretion. The myofibroblasts remodel this tissue through secreted molecules and modulation of their cytoskeleton and specialized con-tractile structures. The non-receptor protein tyrosine kinase Arg (also called Abl2) has the unique ability to bind directly to the actin cytoskeleton, transducing diverse extracellular sig-nals into cytoskeletal rearrangements. In this study we analysed the 1ALCTL and 1BLCTL Arg isoforms in Arg-/- murine embryonal fibroblasts (MEF) cell line, focusing on their capac-ity to activate fibroblasts and to remodel ECM. The results obtained showed that Arg isoform 1BLCTL has a major role in proliferation, migration/invasion of MEF and in inducing a milieu able to modulate tumour cell morphology, while 1ALCTL isoform has a role in MEF adhesion maintaining active focal adhesions. On the whole, the presence of Arg in MEF supports the proliferation, activa-tion, adhesion, ECM contraction and stiffness, while the absence of Arg affected these myofibroblast features

Published
2019

23. Molecular interactions among Arg/abl2, TGFb and Lox and functional role in clear cell Renal Cell Carcinoma (ccRCC) progression

Author

DE MARCO, S, Bianchi, C, Torsello, B, Minutiello, E, Bombelli, S, Grasselli, C, Eriani, S, Zucchini, N, Viganò, P, Strada, G, Perego, R, De Marco Sofia, Bianchi Cristina, Torsello Barbara, Minutiello Emanuela, Bombelli Silvia, Grasselli Chiara, Eriani Stefano, Zucchini Nicola, Viganò Paolo, Strada Giorgio, Perego Roberto, DE MARCO, S, Bianchi, C, Torsello, B, Minutiello, E, Bombelli, S, Grasselli, C, Eriani, S, Zucchini, N, Viganò, P, Strada, G, Perego, R, De Marco Sofia, Bianchi Cristina, Torsello Barbara, Minutiello Emanuela, Bombelli Silvia, Grasselli Chiara, Eriani Stefano, Zucchini Nicola, Viganò Paolo, Strada Giorgio, and Perego Roberto

Published
2019

24. Molecular interaction among TGFb, Lox and Arg/Abl2 in clear cell Renal Cell carcinoma (ccRCC) and in its progression

Author

DE MARCO, S, Torsello, B, Minutiello, E, Bombelli, S, Grasselli, C, Eriani, S, Zucchini, N, Strada, G, Bianchi, C, Perego, R, De Marco Sofia, Torsello Barbara, Minutiello Emanuela, Bombelli Silvia, Grasselli Chiara, Eriani Stefano, Zucchini Nicola, Strada Guido, Bianchi Cristina, Perego Roberto, DE MARCO, S, Torsello, B, Minutiello, E, Bombelli, S, Grasselli, C, Eriani, S, Zucchini, N, Strada, G, Bianchi, C, Perego, R, De Marco Sofia, Torsello Barbara, Minutiello Emanuela, Bombelli Silvia, Grasselli Chiara, Eriani Stefano, Zucchini Nicola, Strada Guido, Bianchi Cristina, and Perego Roberto

Published
2019

25. PKHhigh/CD133+/CD24- stem-like cells isolated from human nephrospheres exibit in vitro multipotency

Author

Bombelli, S, Grasselli, C, Bolognesi, M, Bruno, A, Eriani, S, Torsello, B, DE MARCO, S, Bianchi, C, Strada, G, Zucchini, N, Albini, A, Cattoretti, G, Perego, R, Bombelli Silvia, Grasselli Chiara, Bolognesi maddalena, Bruno Antonino, Eriani Stefano, Torsello barbara, De Marco Sofia, Bianchi Cristina, Strada Guido, Zucchini Nicola, Albini Adriana, Cattoretti Giorgio, Perego Roberto, Bombelli, S, Grasselli, C, Bolognesi, M, Bruno, A, Eriani, S, Torsello, B, DE MARCO, S, Bianchi, C, Strada, G, Zucchini, N, Albini, A, Cattoretti, G, Perego, R, Bombelli Silvia, Grasselli Chiara, Bolognesi maddalena, Bruno Antonino, Eriani Stefano, Torsello barbara, De Marco Sofia, Bianchi Cristina, Strada Guido, Zucchini Nicola, Albini Adriana, Cattoretti Giorgio, and Perego Roberto

Published
2019

27. Role of 1ALCTL and 1BLCTLARG isoforms in the fibroblast activation

Author

Torsello, B, DE MARCO, S, Bombelli, S, Cassina, V, Chisci, E, Bianchi, C, Perego, R, Torsello Barbara, De Marco Sofia, Bombelli Silvia, Cassina valeria, Chisci elisa, Bianchi Cristina, Perego Roberto, Torsello, B, DE MARCO, S, Bombelli, S, Cassina, V, Chisci, E, Bianchi, C, Perego, R, Torsello Barbara, De Marco Sofia, Bombelli Silvia, Cassina valeria, Chisci elisa, Bianchi Cristina, and Perego Roberto

Published
2018

29. Involvement of Annexin A3 isoforms in modulation of lipid storage into clear cell renal cell carcinoma

Author

Bianchi, C, Bombelli, S, DE MARCO, S, Torsello, B, Zucchini, N, Viganò, P, Perego, R, Bianchi Cristina, Bombelli Silvia, De marco Sofia, Torsello Barbara, Zucchini Nicola, Viganò Paolo, Perego Roberto, Bianchi, C, Bombelli, S, DE MARCO, S, Torsello, B, Zucchini, N, Viganò, P, Perego, R, Bianchi Cristina, Bombelli Silvia, De marco Sofia, Torsello Barbara, Zucchini Nicola, Viganò Paolo, and Perego Roberto

Published
2018

30. PKHhigh/CD133+/CD24- stem-like cells isolated from human nephrospheres can be committed to endothelial phoenotype

Author

Bombelli, S, Bolognesi, M, Bruno, A, Torsello, B, DE MARCO, S, Bianchi, C, Viganò, P, Albini, A, Cattoretti, G, Perego, R, Bombelli Silvia, Bolognesi Maddalena, Bruno Antonino, Torsello Barbara, De Marco Sofia, Bianchi Cristina, Viganò Paolo, Albini Adriana, Cattoretti Giorgio, Perego Roberto, Bombelli, S, Bolognesi, M, Bruno, A, Torsello, B, DE MARCO, S, Bianchi, C, Viganò, P, Albini, A, Cattoretti, G, Perego, R, Bombelli Silvia, Bolognesi Maddalena, Bruno Antonino, Torsello Barbara, De Marco Sofia, Bianchi Cristina, Viganò Paolo, Albini Adriana, Cattoretti Giorgio, and Perego Roberto

Published
2018

31. The molecular cross-talk among Arg/Abl2, TGFb and Lox in clear cell Renal Cell Carcinoma progression

Author

DE MARCO, S, Bianchi, C, Torsello, B, Bombelli, S, Zucchini, N, Viganò, P, Perego, R, De marco Sofia, Bianchi Cristina, Torsello Barbara, Bombelli Silvia, Zucchini Nicola, Viganò Paolo, Perego Roberto, DE MARCO, S, Bianchi, C, Torsello, B, Bombelli, S, Zucchini, N, Viganò, P, Perego, R, De marco Sofia, Bianchi Cristina, Torsello Barbara, Bombelli Silvia, Zucchini Nicola, Viganò Paolo, and Perego Roberto

Published
2018

32. Molecular characterization of nephrosphere-derived PKHhigh/CD133+/CD24- Stem-like cells and their use in repopulation of decellularized kidney scaffolds

Author

Bombelli, S, Meregalli, C, Bolognesi, M, Rossetti, G, Ranzani, V, Torsello, B, De Marco, S, Pagani, M, Cattoretti, G, Viganò, P, Bianchi, C, Perego, R, S. Bombelli, C. Meregalli, BOLOGNESI, MADDALENA MARIA, G. Rossetti, V. Ranzani, B. Torsello, S. De Marco, M. Pagani, G. Cattoretti, P. Viganò, C. Bianchi, R. Perego, Bombelli, S, Meregalli, C, Bolognesi, M, Rossetti, G, Ranzani, V, Torsello, B, De Marco, S, Pagani, M, Cattoretti, G, Viganò, P, Bianchi, C, Perego, R, S. Bombelli, C. Meregalli, BOLOGNESI, MADDALENA MARIA, G. Rossetti, V. Ranzani, B. Torsello, S. De Marco, M. Pagani, G. Cattoretti, P. Viganò, C. Bianchi, and R. Perego

Published
2018

33. Nephrosphere-Derived Cells are Induced to Multilineage Differentiation when Cultured on Human Decellularized Kidney Scaffolds

Author

Bombelli, S, Meregalli, C, Scalia, C, Bovo, G, Torsello, B, De Marco, S, Cadamuro, M, Viganò, P, Strada, G, Cattoretti, G, Bianchi, C, Perego, R, Scalia, CR, Torsello, BR, Strada, GR, Perego, R., Bombelli, S, Meregalli, C, Scalia, C, Bovo, G, Torsello, B, De Marco, S, Cadamuro, M, Viganò, P, Strada, G, Cattoretti, G, Bianchi, C, Perego, R, Scalia, CR, Torsello, BR, Strada, GR, and Perego, R.

Abstract

In end-stage chronic kidney disease, the option of organ transplantation is limited due to the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices. Our decellularization protocol enabled us to obtain a completely acellular renal scaffold while maintaining the extracellular matrix structure and composition in terms of collagen IV, laminin, and fibronectin. NS cells, cultured on decellularized renal scaffolds with basal medium, differentiated into proximal and distal tubules as well as endothelium, as highlighted by histology and by the specific expression of epithelial CK 8.18, proximal tubular CD10, distal tubular CK7, and endothelial vWf markers. Endothelial medium promoted the differentiation toward the endothelium, whereas epithelial medium toward epithelium. NS cells seem to be a good tool for scaffold repopulation, paving the way for experimental investigations focused on whole-kidney reconstruction

Published
2018

36. The glucose and lipid metabolism reprogramming is gradedependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation

Author

Bianchi, C, Meregalli, C, Bombelli, S, Di Stefano, V, Salerno, F, Torsello, B, De Marco, S, Bovo, G, Cifola, I, Mangano, E, Battaglia, C, Strada, G, Lucarelli, G, Weiss, R, Perego, R, Weiss, RH, Perego, RA, Bianchi, C, Meregalli, C, Bombelli, S, Di Stefano, V, Salerno, F, Torsello, B, De Marco, S, Bovo, G, Cifola, I, Mangano, E, Battaglia, C, Strada, G, Lucarelli, G, Weiss, R, Perego, R, Weiss, RH, and Perego, RA

Abstract

Clear cell renal cell carcinoma (ccRCC) has a poor prognosis despite novel biological targeted therapies. Tumor aggressiveness and poor survival may correlate with tumor grade at diagnosis and with complex metabolic alterations, also involving glucose and lipid metabolism. However, currently no grade-specific metabolic therapy addresses these alterations. Here we used primary cell cultures from ccRCC of low- and high-grade to investigate the effect on energy state and reduced pyridine nucleotide level, and on viability and proliferation, of specific inhibition of glycolysis with 2-deoxy-D-glucose (2DG), or fatty acid oxidation with Etomoxir. Our primary cultures retained the tissue grade-dependent modulation of lipid and glycogen storage and aerobic glycolysis (Warburg effect). 2DG affected lactate production, energy state and reduced pyridine nucleotide level in high-grade ccRCC cultures, but the energy state only in low-grade. Rather, Etomoxir affected energy state in high-grade and reduced pyridine nucleotide level in low-grade cultures. Energy state and reduced pyridine nucleotide level were evaluated by ATP and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) dye quantification, respectively. 2DG treatment impaired cell proliferation and viability of low-grade ccRCC and normal cortex cultures, whereas Etomoxir showed a cytostatic and cytotoxic effect only in high-grade ccRCC cultures. Our data indicate that in ccRCC the Warburg effect is a grade-dependent feature, and fatty acid oxidation can be activated for different grade-dependent metabolic needs. A possible grade-dependent metabolic therapeutic approach in ccRCC is also highlighted

Published
2017

37. Evaluation of the capability of PKHhigh human adult renal stem-like cells to repopulate human decellularized renal scaffolds

Author

Meregalli, C, Bombelli, S, Bovo, G, Torsello, B, DE MARCO, S, Viganò, P, Cattoretti, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, CATTORETTI, GIORGIO, BIANCHI, CRISTINA, PEREGO, ROBERTO, Meregalli, C, Bombelli, S, Bovo, G, Torsello, B, DE MARCO, S, Viganò, P, Cattoretti, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, CATTORETTI, GIORGIO, BIANCHI, CRISTINA, and PEREGO, ROBERTO

Published
2017

38. Grade-dependent lipid storage in ccRCC cells: molecular and functional study performed in primary cell cultures

Author

Bianchi, C, Meregalli, C, Bombelli, S, Torsello, B, DE MARCO, S, Salerno, F, Cifola, I, Mangano, E, Battaglia, C, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, SALERNO, FABIO ROSARIO, STRADA, GUIDO RAFFAELE, PEREGO, ROBERTO, Bianchi, C, Meregalli, C, Bombelli, S, Torsello, B, DE MARCO, S, Salerno, F, Cifola, I, Mangano, E, Battaglia, C, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, SALERNO, FABIO ROSARIO, STRADA, GUIDO RAFFAELE, and PEREGO, ROBERTO

Published
2017

39. Role of Lysyl oxidase, TGFb1 and Arg tyrosine kinase in invasive and metastatic properties of ccRCC cells

Author

Bianchi, C, DE MARCO, S, Torsello, B, DI STEFANO, V, Meregalli, C, Bombelli, S, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, DE MARCO, SOFIA, TORSELLO, BARBARA ROSA, DI STEFANO, VITALBA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, PEREGO, ROBERTO, Bianchi, C, DE MARCO, S, Torsello, B, DI STEFANO, V, Meregalli, C, Bombelli, S, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, DE MARCO, SOFIA, TORSELLO, BARBARA ROSA, DI STEFANO, VITALBA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, and PEREGO, ROBERTO

Published
2017

40. Repopulation of human decellularized renal scaffolds by renal stem-like cells and progenitors within nephrospheres

Author

Meregalli, C, Bombelli, S, Bovo, G, Torsello, B, DE MARCO, S, Viganò, P, Cattoretti, G, Bianchi, C, Perego, R, Meregalli Chiara, Bombelli Silvia, Bovo Giorgio, Torsello Barbara, De marco Sofia, Viganò Paolo, Cattoretti Giorgio, Bianchi Cristina, Perego roberto, Meregalli, C, Bombelli, S, Bovo, G, Torsello, B, DE MARCO, S, Viganò, P, Cattoretti, G, Bianchi, C, Perego, R, Meregalli Chiara, Bombelli Silvia, Bovo Giorgio, Torsello Barbara, De marco Sofia, Viganò Paolo, Cattoretti Giorgio, Bianchi Cristina, and Perego roberto

Published
2017

43. Endogenous lysyl-oxidase in clear cell renal cell carcinoma promotes tumor progression and collagen stiffness

Author

Torsello, B, Di Stefano, V, Bianchi, C, Battaglia, C, Cifola, I, Mangano, E, Bovo, G, Cassina, V, De Marco, S, Corti, R, Meregalli, C, Bombelli, S, Vigano’, P, Strada, G, Perego, R, TORSELLO, BARBARA ROSA, BIANCHI, CRISTINA, CASSINA, VALERIA, CORTI, ROBERTA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, PEREGO, ROBERTO, Torsello, B, Di Stefano, V, Bianchi, C, Battaglia, C, Cifola, I, Mangano, E, Bovo, G, Cassina, V, De Marco, S, Corti, R, Meregalli, C, Bombelli, S, Vigano’, P, Strada, G, Perego, R, TORSELLO, BARBARA ROSA, BIANCHI, CRISTINA, CASSINA, VALERIA, CORTI, ROBERTA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, and PEREGO, ROBERTO

Published
2016

44. TGF-b1 production is modulated by Arg tyrosine kinase in high glucose treated human renal tubular cells

Author

Bianchi, C, Torsello, B, Meregalli, C, DE MARCO, S, Bovo, G, Brivio, R, Strada, G, Bombelli, S, Perego, R, BIANCHI, CRISTINA, TORSELLO, BARBARA ROSA, MEREGALLI, CHIARA, DE MARCO, SOFIA, BRIVIO, RINALDO, STRADA, GUIDO RAFFAELE, BOMBELLI, SILVIA, PEREGO, ROBERTO, Bianchi, C, Torsello, B, Meregalli, C, DE MARCO, S, Bovo, G, Brivio, R, Strada, G, Bombelli, S, Perego, R, BIANCHI, CRISTINA, TORSELLO, BARBARA ROSA, MEREGALLI, CHIARA, DE MARCO, SOFIA, BRIVIO, RINALDO, STRADA, GUIDO RAFFAELE, BOMBELLI, SILVIA, and PEREGO, ROBERTO

Published
2016

45. Endogenous lysysl oxidase in tumor progression and collagen stiffness: study performed in human clear cell Renal Cell Carcinoma primary cell cultures

Author

Torsello, B, Bianchi, C, Bovo, G, Cassina, V, DE MARCO, S, Meregalli, C, Bombelli, S, Viganò, P, Strada, G, Perego, R, TORSELLO, BARBARA ROSA, BIANCHI, CRISTINA, CASSINA, VALERIA, DE MARCO, SOFIA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, PEREGO, ROBERTO, Torsello, B, Bianchi, C, Bovo, G, Cassina, V, DE MARCO, S, Meregalli, C, Bombelli, S, Viganò, P, Strada, G, Perego, R, TORSELLO, BARBARA ROSA, BIANCHI, CRISTINA, CASSINA, VALERIA, DE MARCO, SOFIA, MEREGALLI, CHIARA, BOMBELLI, SILVIA, STRADA, GUIDO RAFFAELE, and PEREGO, ROBERTO

Published
2016

46. Transcriptomic profiling of multipotent renal nephrosphere PKHhigh cells for the identification of a renal stem signature

Author

Meregalli, C, Bombelli, S, Rossetti, G, Ranzani, V, Torsello, B, DE MARCO, S, Bovo, G, Pagani, M, Cattoretti, G, Strada, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, RANZANI, VALERIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, CATTORETTI, GIORGIO, STRADA, GUIDO RAFFAELE, BIANCHI, CRISTINA, PEREGO, ROBERTO, Meregalli, C, Bombelli, S, Rossetti, G, Ranzani, V, Torsello, B, DE MARCO, S, Bovo, G, Pagani, M, Cattoretti, G, Strada, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, RANZANI, VALERIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, CATTORETTI, GIORGIO, STRADA, GUIDO RAFFAELE, BIANCHI, CRISTINA, and PEREGO, ROBERTO

Published
2016

47. Transcriptomic profile of PKHhigh multipotent renal cells for the identification of a renal stem cell signature

Author

Meregalli, C, Bombelli, S, Rossetti, G, Ranzani, V, Torsello, B, DE MARCO, S, Bovo, G, Pagani, M, Cattoretti, G, Strada, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, RANZANI, VALERIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, PAGANI, MARCO, CATTORETTI, GIORGIO, STRADA, GUIDO RAFFAELE, BIANCHI, CRISTINA, PEREGO, ROBERTO, Meregalli, C, Bombelli, S, Rossetti, G, Ranzani, V, Torsello, B, DE MARCO, S, Bovo, G, Pagani, M, Cattoretti, G, Strada, G, Bianchi, C, Perego, R, MEREGALLI, CHIARA, BOMBELLI, SILVIA, RANZANI, VALERIA, TORSELLO, BARBARA ROSA, DE MARCO, SOFIA, PAGANI, MARCO, CATTORETTI, GIORGIO, STRADA, GUIDO RAFFAELE, BIANCHI, CRISTINA, and PEREGO, ROBERTO

Published
2016

48. Nephrosphere-derived cells cultured on decellularized kidney scaffolds can differentiate into multiple lineages

Author

Bombelli, S, Scalia, C, Meregalli, C, Torsello, B, Bovo, G, Cattoretti, G, Viganò, P, Strada, G, Bianchi, C, Perego, R, BOMBELLI, SILVIA, MEREGALLI, CHIARA, TORSELLO, BARBARA ROSA, CATTORETTI, GIORGIO, BIANCHI, CRISTINA, PEREGO, ROBERTO, Bombelli, S, Scalia, C, Meregalli, C, Torsello, B, Bovo, G, Cattoretti, G, Viganò, P, Strada, G, Bianchi, C, Perego, R, BOMBELLI, SILVIA, MEREGALLI, CHIARA, TORSELLO, BARBARA ROSA, CATTORETTI, GIORGIO, BIANCHI, CRISTINA, and PEREGO, ROBERTO

Published
2015

49. Modulazione del metabolismo lipidico e glicidico in colture cellulari primarie e cancer stem cells in ccRCC: un nuovo approccio per l’identificazione di target terapeutici

Author

Meregalli, C, Bombelli, S, Torsello, B, Bovo, G, Viganò, P, Perego, R, Bianchi, C, Strada, G, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, PEREGO, ROBERTO, BIANCHI, CRISTINA, Strada, G., Meregalli, C, Bombelli, S, Torsello, B, Bovo, G, Viganò, P, Perego, R, Bianchi, C, Strada, G, MEREGALLI, CHIARA, BOMBELLI, SILVIA, TORSELLO, BARBARA ROSA, PEREGO, ROBERTO, BIANCHI, CRISTINA, and Strada, G.

Published
2015

50. Annexin A4 involvement in lipid storage of clear cell Renal Cell Carcinoma

Author

Bianchi, C, Bombelli, S, Meregalli, C, Torsello, B, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, BOMBELLI, SILVIA, MEREGALLI, CHIARA, TORSELLO, BARBARA ROSA, PEREGO, ROBERTO, Bianchi, C, Bombelli, S, Meregalli, C, Torsello, B, Bovo, G, Viganò, P, Strada, G, Perego, R, BIANCHI, CRISTINA, BOMBELLI, SILVIA, MEREGALLI, CHIARA, TORSELLO, BARBARA ROSA, and PEREGO, ROBERTO

Published
2015

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