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Article ; Online: Renal Progenitors Derived from Urine for Personalized Diagnosis of Kidney Diseases.

Mazzinghi, Benedetta / Melica, Maria Elena / Lasagni, Laura / Romagnani, Paola / Lazzeri, Elena

2024 Volume 49, Issue 1, Page(s) 258–265

Abstract: Background: Chronic kidney disease affects 10% of the world population, and it is associated with progression to end-stage kidney disease and increased morbidity and mortality. The advent of multi-omics technologies has expanded our knowledge on the ... ...

Abstract	Background: Chronic kidney disease affects 10% of the world population, and it is associated with progression to end-stage kidney disease and increased morbidity and mortality. The advent of multi-omics technologies has expanded our knowledge on the complexity of kidney diseases, revealing their frequent genetic etiology, particularly in children and young subjects. Genetic heterogeneity and drug screening require patient-derived disease models to establish a correct diagnosis and evaluate new potential treatments and outcomes. Summary: Patient-derived renal progenitors can be isolated from urine to set up proper disease modeling. This strategy allows to make diagnosis of genetic kidney disease in patients carrying unknown significance variants or uncover variants missed from peripheral blood analysis. Furthermore, urinary-derived tubuloids obtained from renal progenitors of patients appear to be potentially valuable for modeling kidney diseases to test ex vivo treatment efficacy or to develop new therapeutic approaches. Finally, renal progenitors derived from urine can provide insights into acute kidney injury and predict kidney function recovery and outcome. Key messages: Renal progenitors derived from urine are a promising new noninvasive and easy-to-handle tool, which improves the rate of diagnosis and the therapeutic choice, paving the way toward a personalized healthcare.
MeSH term(s)	Humans ; Precision Medicine ; Stem Cells ; Kidney Diseases/diagnosis ; Kidney Diseases/urine ; Kidney/pathology ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/urine ; Urine/cytology
Language	English
Publishing date	2024-03-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1326018-2
ISSN	1423-0143 ; 1420-4096
ISSN (online)	1423-0143
ISSN	1420-4096
DOI	10.1159/000538507
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Article: Retinal Microvascular Alterations in Hidradenitis Suppurativa Patients: A Pilot Study Using Optical Coherence Tomography Angiography.

Manfredini, Marco / Ragusa, Emanuele / Gibertini, Matteo / Bigi, Laura / Ferrari, Barbara / Lasagni, Claudia / Magnoni, Cristina / Lazzerini, Andrea / Farnetani, Francesca / Verdina, Tommaso

Journal of clinical medicine

2024 Volume 13, Issue 5

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2024-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13051464
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Article: Treatment and follow-up of genital lichen sclerosus in male children: multidisciplinary management at a tertiary care center.

Paganelli, Alessia / Fabbri, Paolo Viscardo / Ghidini, Filippo / Bigi, Laura / Lasagni, Claudia / Ceccarelli, Pier Luca

Dermatology reports

2023 Volume 15, Issue 4, Page(s) 9774

Language	English
Publishing date	2023-08-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2568735-9
ISSN	2036-7406 ; 2036-7392
ISSN (online)	2036-7406
ISSN	2036-7392
DOI	10.4081/dr.2023.9774
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Article ; Online: Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology.

Melica, Maria Elena / Cialdai, Francesca / La Regina, Gilda / Risaliti, Chiara / Dafichi, Tommaso / Peired, Anna Julie / Romagnani, Paola / Monici, Monica / Lasagni, Laura

Stem cell research & therapy

2024 Volume 15, Issue 1, Page(s) 20

Abstract: Background: The glomerulus is a highly complex system, composed of different interdependent cell types that are subjected to various mechanical stimuli. These stimuli regulate multiple cellular functions, and changes in these functions may contribute to ...

Abstract	Background: The glomerulus is a highly complex system, composed of different interdependent cell types that are subjected to various mechanical stimuli. These stimuli regulate multiple cellular functions, and changes in these functions may contribute to tissue damage and disease progression. To date, our understanding of the mechanobiology of glomerular cells is limited, with most research focused on the adaptive response of podocytes. However, it is crucial to recognize the interdependence between podocytes and parietal epithelial cells, in particular with the progenitor subset, as it plays a critical role in various manifestations of glomerular diseases. This highlights the necessity to implement the analysis of the effects of mechanical stress on renal progenitor cells. Methods: Microgravity, modeled by Rotary Cell Culture System, has been employed as a system to investigate how renal progenitor cells respond to alterations in the mechanical cues within their microenvironment. Changes in cell phenotype, cytoskeleton organization, cell proliferation, cell adhesion and cell capacity for differentiation into podocytes were analyzed. Results: In modeled microgravity conditions, renal progenitor cells showed altered cytoskeleton and focal adhesion organization associated with a reduction in cell proliferation, cell adhesion and spreading capacity. Moreover, mechanical forces appeared to be essential for renal progenitor differentiation into podocytes. Indeed, when renal progenitors were exposed to a differentiative agent in modeled microgravity conditions, it impaired the acquisition of a complex podocyte-like F-actin cytoskeleton and the expression of specific podocyte markers, such as nephrin and nestin. Importantly, the stabilization of the cytoskeleton with a calcineurin inhibitor, cyclosporine A, rescued the differentiation of renal progenitor cells into podocytes in modeled microgravity conditions. Conclusions: Alterations in the organization of the renal progenitor cytoskeleton due to unloading conditions negatively affect the regenerative capacity of these cells. These findings strengthen the concept that changes in mechanical cues can initiate a pathophysiological process in the glomerulus, not only altering podocyte actin cytoskeleton, but also extending the detrimental effect to the renal progenitor population. This underscores the significance of the cytoskeleton as a druggable target for kidney diseases.
MeSH term(s)	Humans ; Weightlessness ; Cytoskeleton/metabolism ; Kidney ; Podocytes ; Kidney Diseases/metabolism ; Stem Cells/metabolism
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-024-03633-3
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Article ; Online: Decellularized Kidney Extracellular Matrix-Based Hydrogels for Renal Tissue Engineering.

Quinteira, Rita / Gimondi, Sara / Monteiro, Nelson O / Sobreiro-Almeida, Rita / Lasagni, Laura / Romagnani, Paola / Neves, Nuno M

Acta biomaterialia

2024

Abstract: Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for ... ...

Abstract	Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture. Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. STATEMENT OF SIGNIFICANCE: The quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2024.04.026
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Article: The Pathology Lesion Patterns of Podocytopathies: How and why?

Ravaglia, Fiammetta / Melica, Maria Elena / Angelotti, Maria Lucia / De Chiara, Letizia / Romagnani, Paola / Lasagni, Laura

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 838272

Abstract: Podocytopathies are a group of proteinuric glomerular disorders driven by primary podocyte injury that are associated with a set of lesion patterns observed on kidney biopsy, i.e., minimal changes, focal segmental glomerulosclerosis, diffuse mesangial ... ...

Abstract	Podocytopathies are a group of proteinuric glomerular disorders driven by primary podocyte injury that are associated with a set of lesion patterns observed on kidney biopsy, i.e., minimal changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis and collapsing glomerulopathy. These unspecific lesion patterns have long been considered as independent disease entities. By contrast, recent evidence from genetics and experimental studies demonstrated that they represent signs of repeated injury and repair attempts. These ongoing processes depend on the type, length, and severity of podocyte injury, as well as on the ability of parietal epithelial cells to drive repair. In this review, we discuss the main pathology patterns of podocytopathies with a focus on the cellular and molecular response of podocytes and parietal epithelial cells.
Language	English
Publishing date	2022-02-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.838272
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Article ; Online: Modeling the Glomerular Filtration Barrier: Are You Kidney-ing Me?

Romagnani, Paola / Lasagni, Laura

Cell stem cell

2017 Volume 21, Issue 1, Page(s) 7–9

Abstract: Podocyte depletion drives kidney disease and kidney failure progression, but podocyte complexity at the glomerular filtration barrier is difficult to model in vitro. In Nature Biomedical Engineering, Musah et al. (2017) developed a multifluidic device ... ...

Abstract	Podocyte depletion drives kidney disease and kidney failure progression, but podocyte complexity at the glomerular filtration barrier is difficult to model in vitro. In Nature Biomedical Engineering, Musah et al. (2017) developed a multifluidic device with iPS-derived podocytes mimicking a functional glomerular filtration barrier that elevates standards for modeling glomerular diseases.
MeSH term(s)	Animals ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Models, Biological ; Podocytes/metabolism ; Podocytes/pathology
Language	English
Publishing date	2017--06
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2017.06.008
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Article ; Online: Molecular Mechanisms of Renal Progenitor Regulation: How Many Pieces in the Puzzle?

Peired, Anna Julie / Melica, Maria Elena / Molli, Alice / Nardi, Cosimo / Romagnani, Paola / Lasagni, Laura

Cells

2021 Volume 10, Issue 1

Abstract: Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments ...

Abstract	Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-like receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single-cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.
MeSH term(s)	Animals ; Humans ; Kidney/cytology ; Models, Biological ; Regeneration ; Stem Cells/cytology
Language	English
Publishing date	2021-01-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10010059
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Article ; Online: Retinoic Acid Benefits Glomerular Organotypic Differentiation from Adult Renal Progenitor Cells In Vitro.

Sobreiro-Almeida, Rita / Melica, Maria Elena / Lasagni, Laura / Romagnani, Paola / Neves, Nuno M

Stem cell reviews and reports

2021 Volume 17, Issue 4, Page(s) 1406–1419

Abstract: When in certain culture conditions, organotypic cultures are able to mimic developmental stages of an organ, generating higher-order structures containing functional subunits and progenitor niches. Despite the major advances in the area, researchers have ...

Abstract	When in certain culture conditions, organotypic cultures are able to mimic developmental stages of an organ, generating higher-order structures containing functional subunits and progenitor niches. Despite the major advances in the area, researchers have not been able to fully recapitulate the complexity of kidney tissue. Pluripotent stem cells are extensively used in the field, but very few studies make use of adult stem cells. Herein, we describe a simple and feasible method for achieving glomerular epithelial differentiation on an organotypic model comprising human renal progenitor cells from adult kidney (hRPCs). Their glomerular differentiative potential was studied using retinoic acid (RA), a fundamental molecule for intermediate mesoderm induction on early embryogenesis. Immunofluorescence, specific cell surface markers expression and gene expression analysis confirm the glomerular differentiative potential of RA in a short-term culture. We also compared the potential of RA with a potent WNT agonist, CHIR99021, on the differentiative capacity of hRPCs. Gene expression and immunofluorescence analysis confirmed that hRPCs are more sensitive to RA stimulation when compared to CHIR9901. Endothelial cells were also included on the spheroids, resulting in a higher organizational level. The assembly potential of these cells and their selective stimulation will give new insights on adult organotypic cell culture studies and will hopefully guide more works in this important area of research.
MeSH term(s)	Adult Stem Cells/cytology ; Cell Differentiation ; Endothelial Cells ; Humans ; Kidney/cytology ; Tretinoin/pharmacology
Chemical Substances	Tretinoin (5688UTC01R)
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-021-10128-8
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Article ; Online: Presentation and progression of MPO-ANCA interstitial lung disease.

Salvati, Lorenzo / Palterer, Boaz / Lazzeri, Elena / Vivarelli, Emanuele / Amendola, Marina / Allinovi, Marco / Caroti, Leonardo / Mazzoni, Alessio / Lasagni, Laura / Emmi, Giacomo / Cavigli, Edoardo / Del Carria, Marco / Di Pietro, Linda / Scavone, Mariangela / Cammelli, Daniele / Lavorini, Federico / Tomassetti, Sara / Rosi, Elisabetta / Parronchi, Paola

Journal of translational autoimmunity

2024 Volume 8, Page(s) 100235

Abstract: The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the ... ...

Abstract	The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.
Language	English
Publishing date	2024-02-23
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-9090
ISSN (online)	2589-9090
DOI	10.1016/j.jtauto.2024.100235
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