Article
Pharmacology & Pharmacy
Kristeen Ye Wen Teo, Shipin Zhang, Jia Tong Loh, Ruenn Chai Lai, Hwee Weng Dennis Hey, Kong-Peng Lam, Sai Kiang Lim, Wei Seong Toh
Summary: MSC exosomes promote the polarization of M2-like macrophages through activation of the toll-like receptor signaling pathway and CD73-mediated adenosine production. The production of adenosine activates AKT/ERK-dependent signaling pathways via binding to adenosine receptors A(2A) and A(2B). These findings highlight the critical role of CD73 in mediating M2-like macrophage polarization by MSC exosomes, and have implications for predicting the immunomodulatory potency of MSC exosome preparations.
Article
Immunology
Anna Maria Tolomeo, Ignazio Castagliuolo, Martina Piccoli, Michele Grassi, Fabio Magarotto, Giada De Lazzari, Ricardo Malvicini, Federico Caicci, Chiara Franzin, Melania Scarpa, Veronica Macchi, Raffaele De Caro, Imerio Angriman, Antonella Viola, Andrea Porzionato, Michela Pozzobon, Maurizio Muraca
Summary: The study compared the effects of MSCs and MSC-EVs in mice with experimental colitis, finding that EVs had a better therapeutic effect than MSCs, with a more predictable behavior, a safer therapeutic profile, and a higher therapeutic efficacy compared to their parent cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Angelos Matheakakis, Aristea Batsali, Helen A. Papadaki, Charalampos G. Pontikoglou
Summary: Mesenchymal stromal cells (MSCs) are multipotent stem cells with potential applications in tissue repair and treatment of autoimmune disorders. MSC-EVs play a key role in intercellular communication by carrying various signaling factors, exhibiting immunomodulatory potential, and emerging as an appealing alternative therapeutic option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Szabolcs Muzsai, Ore-Matan Maryanovsky, Roland Ander, Gabor Koncz, Anett Mazlo, Attila Bacsi, Marta Toth
Summary: The cell-free supernatant (CFS) derived from Lactobacillus casei (L. casei), a member of human microbiota, enhances the sensitivity of mesenchymal-stromal-cell-like (MSCI) cells to viral stimuli and induces the development of dendritic cells (DCs) with anti-inflammatory and antiviral properties through pretreated MSCl cells. The presence of L. casei-derived extracellular vesicles in CFS during pretreatment is crucial for the production of INF & beta; and CXCL10 by MSCl cells upon viral stimulation. Moreover, L. casei CFS and/or poly (I:C)-conditioned MSCI cells alter the differentiation process and functional activities of freshly isolated monocytes and developing DCs.
Article
Biochemistry & Molecular Biology
Rebecca Davies, Shannen Allen, Claire Mennan, Mark Platt, Karina Wright, Oksana Kehoe
Summary: The immunomodulatory properties of MSCs can be replicated by their extracellular vesicles (EVs), but it is difficult to distinguish the true capabilities of MSC EVs from contaminating bovine EVs and protein derived from supplemental foetal bovine serum (FBS). Different FBS EV depletion protocols have varying depletion efficiency, which can negatively impact the cell phenotype. This study investigates the impact of various FBS EV depletion strategies on umbilical cord MSC characteristics, and cautions on the use of highly efficient EV depletion protocols, as it can affect the MSC phenotype and immunomodulatory properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Qian Huai, Cheng Zhu, Xu Zhang, Hanren Dai, Xiaolei Li, Hua Wang
Summary: Liver disease is a major global cause of death and disability. Chronic liver inflammation and fibrosis can result from various insults, leading to irreversible dysfunction. Liver transplantation is currently the last resort for end-stage liver disease, but faces challenges. Mesenchymal stromal/stem cells (MSCs) offer a promising alternative with anti-inflammatory and immunomodulatory properties. This review discusses the characteristics of MSCs and their potential mechanism in liver disease treatment, as well as strategies to enhance their therapeutic properties. The clinical application of MSCs and their extracellular vesicles in liver diseases is also explored.
CELL AND BIOSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Rui Alvites, Mariana Branquinho, Ana C. Sousa, Bruna Lopes, Patricia Sousa, Ana Colette Mauricio
Summary: Mesenchymal Stem/Stromal Cells (MSCs) have high clinical value and have been extensively studied. Their immunomodulatory influence occurs through both direct and paracrine routes, but the mechanisms are not fully understood. This review summarizes the immunoregulatory capacity of MSCs and their secretion products, with a focus on migration, homing, direct cell action, and paracrine activity, and explores related techniques.
Review
Medicine, Research & Experimental
Carolina Soler-Botija, Marta Monguio-Tortajada, Micaela Munizaga-Larroude, Carolina Galvez-Monton, Antoni Bayes-Genis, Santiago Roura
Summary: Extracellular vesicles (EVs), as means of cellular communication, carry immunomodulatory and pro-regenerative cargoes. Treatments focused on MSC-EVs have versatile potential in modulating inflammatory-related conditions, but important concerns need to be addressed.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Tamiris Borges da Silva, Erika Rendra, Christopher A. W. David, Karen Bieback, Michael J. Cross, Bettina Wilm, Neill J. Liptrott, Patricia Murray
Summary: HUC-MSC-derived extracellular vesicles do not alter the surface marker expression of macrophages but promote angiogenesis and phagocytic capacity.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell Biology
Jessica Altemus, Neda Dadgar, Yan Li, Amy L. Lightner
Summary: The breakdown of gastrointestinal tract immune homeostasis leads to Crohn's disease (CD). Mesenchymal stem cells (MSCs) have demonstrated clinical efficacy in treating CD. This study investigated the interaction between adipose-derived MSCs and macrophages, and found that MSCs and their derived extracellular vesicles (EVs) can regulate macrophage polarization and promote the differentiation of monocytes into pro-inflammatory M1 phenotype in CD patients. Conversely, MSCs and their derived EVs from healthy individuals can drive monocytes to an anti-inflammatory M2 subset, suggesting the potential therapeutic use of MSCs and EVs in CD treatment.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bin Zhang, Ruenn Chai Lai, Wei Kian Sim, Sai Kiang Lim
Summary: The study suggests that mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) could be potential biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA). MSC-sEVs can reduce disease progression, disease severity, inflammation, and joint damage by increasing anti-inflammatory M2 macrophages and decreasing pro-inflammatory M1 macrophages.
Article
Biochemistry & Molecular Biology
Natalia G. Blanco, Natalia M. Machado, Ligia L. L. Castro, Mariana A. A. Antunes, Christina M. M. Takiya, Monique R. O. Trugilho, Luana R. R. Silva, Adriana F. Paes F. Leme, Romenia R. Domingues, Bianca A. A. Pauletti, Beatriz T. T. Miranda, Johnatas D. D. Silva, Claudia C. C. dos Santos, Pedro L. L. Silva, Patricia R. M. Rocco, Fernanda F. F. Cruz
Summary: The effects of different sources of MSC-derived extracellular vesicles (EVs), including those obtained from bone marrow (BM), adipose (AD), or lung (L) tissues, on sepsis were investigated. The proteome analysis of EVs revealed that BM-EVs were associated with less organ damage compared with AD-EVs and L-EVs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Fabiany da Costa Goncalves, Sander S. Korevaar, Maitane Ortiz Virumbrales, Carla C. Baan, Marlies E. J. Reinders, Ana Merino, Eleuterio Lombardo, Martin J. Hoogduijn
Summary: Mesenchymal stromal cells (MSC) show promise as a therapy for inflammatory diseases, but their large size leads to entrapment in the lungs after intravenous infusion, limiting their effectiveness. Researchers have developed nanometer-sized particles from MSC membranes (membrane particles, MP) to extend the reach of MSC immunoregulatory therapy beyond the lungs. These particles exhibit immunomodulatory properties and are taken up by macrophages and human umbilical vein endothelial cells (HUVEC) in a dose, time, and temperature-dependent manner. The uptake of MP depends on specific endocytic pathways and is influenced by cell type and inflammatory conditions, with anti-inflammatory M2 macrophages showing increased uptake compared to pro-inflammatory M1 macrophages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Cassia Lisboa Braga, Renata Trabach Santos, Carla Medeiros da Silva, Nazareth de Novaes Rocha, Nathane Santanna Felix, Mayck Medeiros, Monique Martins Melo, Johnatas Dutra Silva, Douglas Esteves Teixeira, Celso Caruso Neves, Patricia Rieken Macedo Rocco, Fernanda Ferreira Cruz, Pedro Leme Silva
Summary: This study evaluated the preconditioning effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and their extracellular vesicles (EVs) in experimental pulmonary arterial hypertension (PAH). The results showed that BM-MSCs and EVs preconditioned under normoxia or hypoxia were effective in reducing right ventricular pressure, perivascular collagen content, and vascular wall thickness in PAH rats. Additionally, they also played a positive role in improving endothelial to mesenchymal transition.
Review
Immunology
Sylwia Dabrowska, Anna Andrzejewska, Miroslaw Janowski, Barbara Lukomska
Summary: Mesenchymal stem cells (MSCs) possess supportive, differentiating, and immunoregulatory functions, while the extracellular vesicles (EVs) they produce can serve as a potential cellular therapy tool.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Hernan Gonzalez-King, Sandra Tejedor, Maria Ciria, Marta Gil-Barrachina, Mario Soriano-Navarro, Rafael Sanchez-Sanchez, Pilar Sepulveda, Nahuel A. Garcia
Summary: This study investigates the involvement of small extracellular vesicles (SEVs) in functional Notch signaling and finds that SEVs in breast cancer cells can regulate Notch signal transduction, leading to increased invasiveness and proliferation of breast cancer cells.
CANCER GENE THERAPY
(2022)
Letter
Hematology
Lidia M. Fernandez-Sevilla, German Belenguer, Beatriz Marti-Prado, Paula Ortiz-Sanchez, Manuel Ramirez, Alberto Varas, Isabel Farinas, Angeles Vicente
Article
Chemistry, Applied
O. Gil-Castell, I Ontoria-Oviedo, J. D. Badia, E. Amaro-Prellezo, P. Sepulveda, A. Ribes-Greus
Summary: Electrospun nanofibers based on polycaprolactone and gelatin, with the addition of polyaniline particles, were prepared. Controlled hydrolytic action on the polycaprolactone resulted in changes in molecular mass, crystalline structure, and surface morphology. Increased dissolution time and gelatin percentage improved degradability and biocompatibility. The addition of polyaniline promoted increased electrical conductivity and cardiomyocyte proliferation.
REACTIVE & FUNCTIONAL POLYMERS
(2022)
Correction
Cell & Tissue Engineering
Imelda Ontoria-Oviedo, Itziar Palacios, Joaquin Panadero, Belen Sanchez, Francisco Garcia-Garcia, Adolfo Lopez-Cerdan, Akaitz Dorronsoro, Delia Castellano, Luis Rodriguez-Borlado, Antonio Bernad, Pilar Sepulveda
STEM CELLS INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Diego Herrero, Guillermo Albericio, Marina Higuera, Maria Herranz-Lopez, Miguel A. Garcia-Brenes, Alejandra Cordero, Enrique Roche, Pilar Sepulveda, Carmen Mora, Antonio Bernad
Summary: Research on the interaction of adult cardiac progenitor cells with other cardiac cell populations can define the vascular cardiac stem cell niche, which is associated with low oxidative stress domains in vasculature, and manipulating this niche may offer new hope in the cardiac regeneration field.
Review
Immunology
Maria Eugenia Fernandez-Santos, Mariano Garcia-Arranz, Enrique J. Andreu, Ana Maria Garcia-Hernandez, Miriam Lopez-Parra, Eva Villaron, Pilar Sepulveda, Francisco Fernandez-Aviles, Damian Garcia-Olmo, Felipe Prosper, Fermin Sanchez-Guijo, Jose M. Moraleda, Agustin G. Zapata
Summary: This article reviews the current applications of MSCs in cell-based therapies and analyzes the methods of manufacturing and handling these cells, including pre-conditioning, cell homing, immunomodulation, etc. It also provides guidelines for intermediate quality control according to European and US regulations.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ana de la Fuente, Marta Santisteban, Josep Lupon, Jose Manuel Aramendia, Agnes Diaz, Ana Santaballa, Amparo Hernandiz, Pilar Sepulveda, German Cediel, Begona Lopez, Jose Maria Lopez Picazo, Manuel M. Mazo, Gregorio Rabago, Juan Jose Gavira, Ignacio Garcia-Bolao, Javier Diez, Arantxa Gonzalez, Antoni Bayes-Genis, Susana Ravassa
Summary: Elevated levels of procollagen type I C-terminal propeptide (PICP), a biomarker of myocardial fibrosis, are associated with early subclinical left ventricular dysfunction (LVD) and predict later development of cardiotoxicity in patients treated with anthracycline-based cancer chemotherapy (ACC). PICP is also associated with LVD in ACC-induced heart failure patients. These findings provide valuable insights into the mechanisms of LVD after ACC and suggest PICP as a promising tool for monitoring cardiotoxicity.
Article
Biochemistry & Molecular Biology
Imelda Ontoria-Oviedo, Elena Amaro-Prellezo, Delia Castellano, Elena Venegas-Venegas, Fernando Gonzalez-Santos, Amparo Ruiz-Sauri, Beatriz Pelacho, Felipe Prosper, Maria Dolores Perez del Caz, Pilar Sepulveda
Summary: Impaired wound healing in patients with type 2 diabetes is characterized by chronic inflammation. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules that regulate inflammation. This study found that LIPINOVA(R), a nutritional supplement rich in SPMs and EPA, promotes wound healing by reducing inflammation and inducing angiogenesis and macrophage polarization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Araceli Lerida-Viso, Alejandra Estepa-Fernandez, Angela Morella-Aucejo, Beatriz Lozano-Torres, Maria Alfonso, Juan F. Blandez, Viviana Bisbal, Pilar Sepulveda, Alba Garcia-Fernandez, Mar Orzaez, Ramon Martinez-Manez
Summary: Many anticancer drugs can cause premature aging in healthy tissues, resulting in accelerated aging processes and adverse effects in patients. Cardiotoxicity is a major limiting factor in the use of doxorubicin as a cancer treatment, leading to long-term morbidity and mortality. In this study, it was demonstrated that induction of senescence in the heart contributes to impaired cardiac function in mice treated with doxorubicin. Elimination of senescent cells using the senolytic Navitoclax significantly reduced senescence and cardiotoxicity markers, and restored cardiac function in mice. These results suggest the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced by chemotherapy.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Rafael Sanchez-Sanchez, Ignacio Reinal, Esteban Peiro-Molina, Marc Buigues, Sandra Tejedor, Amparo Hernandiz, Marta Selva, David Hervas, Antonio J. Canada, Akaitz Dorronsoro, Ana Santaballa, Carmen Salvador, Florian Caiment, Jos Kleinjans, Luis Martinez-Dolz, Isabel Moscoso, Ricardo Lage, Jose R. Gonzalez-Juanatey, Joaquin Panadero, Ernesto Aparicio-Puerta, Antonio Bernad, Pilar Sepulveda
Summary: This study investigated the clinical data of breast cancer patients receiving anthracycline chemotherapy and found that miR-4732-3p is a novel biomarker of cardiotoxicity and may have therapeutic potential against anthracycline-induced heart damage.
Article
Multidisciplinary Sciences
Marcha Verheijen, Ugis Sarkans, Witold Wolski, Danyel Jennen, Florian Caiment, Jos Kleinjans
Summary: The data obtained from in vitro experiments includes multi-omics data, functional endpoints measurements, as well as additional multi-omics data from human biopsies. These data are valuable for drug safety assessment and related research.
Article
Biochemical Research Methods
Aaron Boughbina-Portoles, Lorenzo Sanjuan-Navarro, Lusine Hakobyan, Marta Gomez-Ferrer, Yolanda Moliner-Martinez, Pilar Sepulveda, Pilar Campins-Falco
Summary: Carbon black nanomaterial (CB-NM) is widely used in industries and poses a high risk of exposure, requiring assessment of its health impact. In this study, asymmetric flow field-flow fractionation (AF4) coupled with UV-Vis and dynamic light scattering (DLS) detectors was used to optimize the dispersion of CB in cell culture media. The presence of a non-ionic surfactant combined with cell culture media significantly improved dispersion stability, resulting in shorter particles and more favorable zeta potential values. Additionally, the presence of amino acids in the culture media enhanced the monodispersity and stability of CB dispersions.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Letter
Dermatology
Rosa Sacedon, M. Carmen de Arriba, Lucia Martinez-Santamaria, Rocio Maseda, Sara Herraiz-Gil, Eva Jimenez, Isabel Rosales, Lucia Quintana, Nuria Illera, Marta Garcia, Nora Butta, Ihosvany Fernandez-Bello, Su M. Lwin, Miguel Fernandez-Arquero, Carlos Leon, John A. Mcgrath, M. Angeles Vicente, Marcela del Rio, Raul de Lucas, Silvia Sanchez-Ramon, Maria Jose Escamez
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Review
Cell Biology
Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, Maria Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masia
Summary: Chronic inflammation in inflammatory bowel disease (IBD) can lead to tissue damage and remodeling, ultimately resulting in fibrosis. Epithelial cells play a key role in fibrosis by promoting fibroblast activation and extracellular matrix deposition. Additionally, epithelial cells can undergo epithelial-mesenchymal transition and directly contribute to fibroblast activation and extracellular matrix deposition. Understanding these complex interactions may provide new therapeutic targets for preventing or treating fibrosis in IBD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ignacio Reinal, Imelda Ontoria-Oviedo, Marta Selva, Marilu Casini, Esteban Peiro-Molina, Carlos Fambuena-Santos, Andreu M. M. Climent, Julia Balaguer, Adela Canete, Jaume Mora, Angel Raya, Pilar Sepulveda
Summary: Anthracyclines are commonly used to treat solid cancers, but their effectiveness is hindered by cardiotoxicity. As the number of pediatric cancer survivors increases, more people are living with anthracycline-induced cardiotoxicity, highlighting the need for new models to understand the mechanisms of this damage.