IF 5.1 2区生物学

Cells Pub Date : 2025-03-19 DOI: 10.3390/cells14060458

Gabriele Storti, Riccardo Foti, Roberta Foti, Marco Palmesano, Martina Patacchiola, Dalila Incognito, Giulio Cervelli, Benedetto Longo, Maria Giovanna Scioli, Elena Fiorelli, Sonia Terriaca, Andrea Lisa, Bong Sung Kim, Augusto Orlandi, Valerio Cervelli

{"title":"A Comprehensive Exploration of the Biological Effects of Adipose-Derived Stem Cells in the Treatment of Systemic Sclerosis.","authors":"Gabriele Storti, Riccardo Foti, Roberta Foti, Marco Palmesano, Martina Patacchiola, Dalila Incognito, Giulio Cervelli, Benedetto Longo, Maria Giovanna Scioli, Elena Fiorelli, Sonia Terriaca, Andrea Lisa, Bong Sung Kim, Augusto Orlandi, Valerio Cervelli","doi":"10.3390/cells14060458","DOIUrl":"10.3390/cells14060458","url":null,"abstract":"Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy and tissue fibrosis affecting the skin and internal organs. Genetic and environmental factors influence susceptibility, severity, and onset. Current treatments are limited and not always effective, leading researchers to investigate new approaches, such as the use of adipose-derived mesenchymal stem cells (ADSCs) through fat grafting. This review seeks to understand how ADSCs may impact the development and progression of SSc, with a particular focus on how these cells could alter immune responses and reduce fibrosis. ADSCs have been found to affect various immune cells, including T cells, B cells, macrophages, and dendritic cells, by releasing cytokines, chemokines, and growth factors. These interactions generally suppress inflammation and promote a regulatory immune environment. Additionally, ADSCs can influence the extracellular matrix, helping to prevent fibrosis through signaling molecules like exosomes. ADSCs show promise as a treatment for SSc due to their ability to modulate the immune system and reduce fibrosis. Early clinical studies are encouraging, but more research is needed to fully understand how they work and to develop effective treatment protocols.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ciliary Ion Channels in Polycystic Kidney Disease.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-19 DOI: 10.3390/cells14060459

Lubna A Alshriem, Raghad Buqaileh, Qasim Alorjani, Wissam AbouAlaiwi

{"title":"Ciliary Ion Channels in Polycystic Kidney Disease.","authors":"Lubna A Alshriem, Raghad Buqaileh, Qasim Alorjani, Wissam AbouAlaiwi","doi":"10.3390/cells14060459","DOIUrl":"10.3390/cells14060459","url":null,"abstract":"Polycystic kidney disease (PKD) is the most common hereditary disorder that disrupts renal function and frequently progresses to end-stage renal disease. Recent advances have elucidated the critical role of primary cilia and ciliary ion channels, including transient receptor potential (TRP) channels, cystic fibrosis transmembrane conductance regulator (CFTR), and polycystin channels, in the pathogenesis of PKD. While some channels primarily function as chloride conductance channels (e.g., CFTR), others primarily regulate calcium (Ca+2) homeostasis. These ion channels are essential for cellular signaling and maintaining the normal kidney architecture. Dysregulation of these pathways due to genetic mutations in PKD1 and PKD2 leads to disrupted Ca+2 and cAMP signaling, aberrant fluid secretion, and uncontrolled cellular proliferation, resulting in tubular cystogenesis. Understanding the molecular mechanisms underlying these dysfunctions has opened the door for innovative therapeutic strategies, including TRPV4 activators, CFTR inhibitors, and calcimimetics, to mitigate cyst growth and preserve renal function. This review summarizes the current knowledge on the roles of ciliary ion channels in PKD pathophysiology, highlights therapeutic interventions targeting these channels, and identifies future research directions for improving patient outcomes.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysregulation of T Follicular Helper and Regulatory Cells in IRF5-SLE Homozygous Risk Carriers and Systemic Lupus Erythematosus Patients.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-19 DOI: 10.3390/cells14060454

Bharati Matta, Lydia Thomas, Vinay Sharma, Betsy J Barnes

引用次数: 0

A Cost-Effective and Easy to Assemble 3D Human Microchannel Blood-Brain Barrier Model and Its Application in Tumor Cell Adhesion Under Flow.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-19 DOI: 10.3390/cells14060456

Yunfei Li, Bingmei M Fu

{"title":"A Cost-Effective and Easy to Assemble 3D Human Microchannel Blood-Brain Barrier Model and Its Application in Tumor Cell Adhesion Under Flow.","authors":"Yunfei Li, Bingmei M Fu","doi":"10.3390/cells14060456","DOIUrl":"10.3390/cells14060456","url":null,"abstract":"By utilizing polydimethylsiloxane (PDMS), collagen hydrogel, and a cell line for human cerebral microvascular endothelial cells, we produced a 3D microchannel blood-brain barrier (BBB) model under physiological flow. This 3D BBB has a circular-shaped cross-section and a diameter of ~100 μm, which can properly mimic the cerebral microvessel responsible for material exchange between the circulating blood and brain tissue. The permeability of the 3D microchannel BBB to a small molecule (sodium fluorescein with a molecular weight of 376) and that to a large molecule (Dex-70k) are the same as those of rat cerebral microvessels. This 3D BBB model can replicate the effects of a plasma protein, orosomucoid, a cytokine, vascular endothelial growth factor (VEGF), and an enzyme, heparinase III, on either rat cerebral or mesenteric microvessesels in terms of permeability and the modulation of glycocalyx (heparan sulfate). It can also replicate the adhesion of a breast cancer cell, MDA-MB-231, in rat mesenteric microvessels under no treatment or treatments with VEGF, orosomucoid, and heparinase III. Because of difficulties in accessing human cerebral microvessels, this inexpensive and easy to assemble 3D human BBB model can be applied to investigate BBB-modulating mechanisms in health and in disease and to develop therapeutic interventions targeting tumor metastasis to the brain.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Colorectal Organoids: Models, Imaging, Omics, Therapy, Immunology, and Ethics.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-19 DOI: 10.3390/cells14060457

Martina Taglieri, Linda Di Gregorio, Serena Matis, Chiara Rosa Maria Uras, Massimo Ardy, Sara Casati, Monica Marchese, Alessandro Poggi, Lizzia Raffaghello, Roberto Benelli

引用次数: 0

Cell Homeostasis or Cell Death-The Balancing Act Between Autophagy and Apoptosis Caused by Steatosis-Induced Endoplasmic Reticulum (ER) Stress.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-18 DOI: 10.3390/cells14060449

Anna Stilkerich, Gerda Schicht, Lena Seidemann, René Hänsel, Adrian Friebel, Stefan Hoehme, Daniel Seehofer, Georg Damm

{"title":"Cell Homeostasis or Cell Death-The Balancing Act Between Autophagy and Apoptosis Caused by Steatosis-Induced Endoplasmic Reticulum (ER) Stress.","authors":"Anna Stilkerich, Gerda Schicht, Lena Seidemann, René Hänsel, Adrian Friebel, Stefan Hoehme, Daniel Seehofer, Georg Damm","doi":"10.3390/cells14060449","DOIUrl":"10.3390/cells14060449","url":null,"abstract":"Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition with potential progression to cirrhosis and impaired regeneration post-resection. A key mechanism underlying lipotoxicity is endoplasmic reticulum (ER) stress, particularly the activation of the unfolded protein response (UPR). This study investigates the interplay between lipid accumulation, endoplasmic reticulum (ER) stress, and cellular outcomes, focusing on the balance between autophagy and apoptosis. We cultured primary human hepatocytes (PHH) in a free fatty acid (FFA)-enriched medium for 120 h, assessing lipid accumulation, metabolism, and the expression of selected UPR markers. Additionally, we investigated the effects of lipid load on cell activity and growth in proliferating HepG2 cells. We observed that FFA uptake consistently induced ER stress, shifting cellular responses toward apoptosis under high lipid loads. Donor-specific differences were evident, particularly in lipid storage, excretion, and sensitivity to lipotoxicity. Some donors exhibited limited triglyceride (TAG) storage and excretion, leading to an excess of FFA whose metabolic fate remains unclear. Proliferation was more sensitive to lipid accumulation than overall cell activity, with even low FFA concentrations impairing growth, highlighting the vulnerability of regenerative processes to steatosis. The study elucidates how ER stress pathways, such as PERK-CHOP and IRE1α-JNK, are differentially activated in response to lipid overload, tipping the balance toward apoptosis in severe cases. The limited activation of repair mechanisms, such as autophagy, further emphasizes the critical role of ER stress in determining hepatocyte fate. The donor-dependent variability highlights the need for personalized strategies to mitigate lipotoxic effects and enhance liver regeneration in steatosis-related conditions.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterisation of Cytotoxicity-Related Receptors on γδ T Cells in Chronic Lymphocytic Leukaemia.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-18 DOI: 10.3390/cells14060451

Michał Zarobkiewicz, Natalia Lehman, Izabela Morawska-Michalska, Adam Michalski, Wioleta Kowalska, Agata Szymańska, Waldemar Tomczak, Agnieszka Bojarska-Junak

{"title":"Characterisation of Cytotoxicity-Related Receptors on γδ T Cells in Chronic Lymphocytic Leukaemia.","authors":"Michał Zarobkiewicz, Natalia Lehman, Izabela Morawska-Michalska, Adam Michalski, Wioleta Kowalska, Agata Szymańska, Waldemar Tomczak, Agnieszka Bojarska-Junak","doi":"10.3390/cells14060451","DOIUrl":"10.3390/cells14060451","url":null,"abstract":"Chronic lymphocytic leukaemia (CLL) is a haematological malignancy primarily affecting older adults, characterised by the proliferation of functionally impaired B lymphocytes with abnormal expression of CD5, a typical T cell marker. The current study investigates the expression of cytotoxicity-related receptors (CD16, CD56, CD57, CD69) and a checkpoint (LAG-3) on γδ T cells in CLL patients. Sixty-nine treatment-naive CLL patients and fourteen healthy controls were recruited. Flow cytometry analysis revealed that the CLL patients had higher expressions of CD56 and LAG-3 and lower CD16 on their γδ T cells compared to the healthy controls. Subgroup analysis showed that ZAP-70-negative patients exhibited increased CD69, while CD38-negative patients showed higher CD16 expression. Additionally, CD16 expression was inversely correlated with serum LDH levels, a marker of disease progression. Bioinformatic analysis of the LAG-3 ligand mRNA in a CLL dataset indicated higher expression of HLA-DQA2 and HLA-DRB5 in patients with unmutated IGVH. Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomaterial Properties and Differentiation Strategies for Tenogenic Differentiation of Mesenchymal Stem Cells.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-18 DOI: 10.3390/cells14060452

Brendon Roets, Heidi Abrahamse, Anine Crous

{"title":"Biomaterial Properties and Differentiation Strategies for Tenogenic Differentiation of Mesenchymal Stem Cells.","authors":"Brendon Roets, Heidi Abrahamse, Anine Crous","doi":"10.3390/cells14060452","DOIUrl":"10.3390/cells14060452","url":null,"abstract":"Tendinopathy is a prevalent musculoskeletal condition that affects both aging populations and individuals involved in repetitive, high-intensity activities, such as athletes. Current treatment options primarily address symptom management or involve surgery, which carries a significant risk of complications and re-injury. This highlights the need for regenerative medicine approaches that combine stem cells, biomaterials, and growth factors. However, achieving effective tenogenic differentiation remains challenging due to the absence of standardized differentiation protocols. Consequently, a review of existing research has been conducted to identify optimal biomaterial properties and growth factor protocols. Findings suggest that the ideal biomaterial for tenogenic differentiation should feature a 3D structure to preserve tenogenic expression, incorporate a combination of aligned micro- and nanofibers to promote differentiation, and require further investigation into optimal stiffness. Additionally, growth factor protocols should include an induction phase to initiate tenogenic lineage commitment, followed by a maintenance phase to support matrix production and maturation.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-18 DOI: 10.3390/cells14060450

Ruben Verloy, Angela Privat-Maldonado, Jonas Van Audenaerde, Sophie Rovers, Hannah Zaryouh, Jorrit De Waele, Delphine Quatannens, Dieter Peeters, Geert Roeyen, Christophe Deben, Evelien Smits, Annemie Bogaerts

{"title":"Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation.","authors":"Ruben Verloy, Angela Privat-Maldonado, Jonas Van Audenaerde, Sophie Rovers, Hannah Zaryouh, Jorrit De Waele, Delphine Quatannens, Dieter Peeters, Geert Roeyen, Christophe Deben, Evelien Smits, Annemie Bogaerts","doi":"10.3390/cells14060450","DOIUrl":"10.3390/cells14060450","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) presents significant treatment challenges due to its desmoplastic reaction, which impedes therapeutic effectiveness, highlighting the need for advanced vitro models to better mimic the complex tumor environment. The current three-dimensional co-culture models of fibroblasts and endothelial cells are lacking, which presents a challenge for performing more comprehensive in vitro research. Our study developed triple co-culture spheroid models using MiaPaCa-2 and BxPC-3 cancer cell lines, with RLT-PSC and hPSC21 pancreatic stellate cell lines and the endothelial cell line HMEC-1. These models were assessed through growth assays, multicolor flow cytometry to optimize cell ratios, cell viability assays to evaluate drug responses, and a tube formation assay with a spheroid-conditioned medium to examine angiogenesis. Our triple co-culture spheroids effectively replicate the PDAC microenvironment, showing significant variations in drug responses influenced by cellular composition, density, and spatial arrangement. The tube formation assay showcased the potential of our models to quantitatively assess a treatment-induced angiogenic response. These cost-effective triple-co-culture in vitro spheroid models provide vital insights into the PDAC microenvironment, significantly improving the quality of the in vitro evaluation of treatment responses.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Recovery of Epidermal Proliferation Pattern in Human Skin Xenograft.

IF 5.1 2区生物学

Cells Pub Date : 2025-03-17 DOI: 10.3390/cells14060448

Olga Cherkashina, Alexandra Tsitrina, Danila Abolin, Elena Morgun, Anastasiya Kosykh, Marat Sabirov, Ekaterina Vorotelyak, Ekaterina Kalabusheva

{"title":"The Recovery of Epidermal Proliferation Pattern in Human Skin Xenograft.","authors":"Olga Cherkashina, Alexandra Tsitrina, Danila Abolin, Elena Morgun, Anastasiya Kosykh, Marat Sabirov, Ekaterina Vorotelyak, Ekaterina Kalabusheva","doi":"10.3390/cells14060448","DOIUrl":"10.3390/cells14060448","url":null,"abstract":"Abnormalities in epidermal keratinocyte proliferation are a characteristic feature of a range of dermatological conditions. These include hyperproliferative states in psoriasis and dermatitis as well as hypoproliferative states in chronic wounds. This emphasises the importance of investigating the proliferation kinetics under conditions of healthy skin and identifying the key regulators of epidermal homeostasis, maintenance, and recovery following wound healing. Animal models contribute to our understanding of human epidermal self-renewal. Human skin xenografting overcomes the ethical limitations of studying human skin during regeneration. The application of this approach has allowed for the identification of a single population of stem cells and both slowly and rapidly cycling progenitors within the epidermal basal layer and the mapping of their location in relation to rete ridges and hair follicles. Furthermore, we have traced the dynamics of the proliferation pattern reorganization that occurs during epidermal regeneration, underlining the role of YAP activity in epidermal relief formation.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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