Review on new approach methods to gain insight into the feto-maternal interface physiology DOI Creative Commons
Ramkumar Menon, Louis J. Muglia,

Lisa Hara Levin

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 30, 2023

Non-human animals represent a large and important feature in the history of biomedical research. The validity their use, terms reproducible outcomes translational confidence to human situation, as well ethical concerns surrounding that have been remain controversial topics. Over last 10 years, communities developing microphysiological systems (MPS) produced new approach method (NAMs) such organoids organs-on-a-chip. These alternative methodologies shown indications greater reliability translatability than animal use some areas, more humane substitutions for these settings, - with continued scientific effort may change conduct basic research, clinical studies, safety testing, drug development. Here, we present an introduction human-relevant suggest how suite pregnancy associated feto-maternal interface system-oriented NAMs be integrated reliable partial-/full replacements investigators, significantly aid animal-/environmental welfare, improve healthcare outcomes.

Language: Английский

Scaffold-based 3D cell culture models in cancer research DOI Creative Commons
Waad H. Abuwatfa, William G. Pitt, Ghaleb A. Husseini

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Jan. 14, 2024

Abstract Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) culture systems. In 3D cultures, cells are grown an environment that more closely mimics the architecture and complexity of vivo tumors. This approach has revolutionized research by providing a accurate representation tumor microenvironment (TME) enabling study behavior response to therapies physiologically relevant context. One key benefits is ability recapitulate complex interactions between their surrounding stroma. Tumors consist not only but also various other types, including stromal cells, immune blood vessels. These models bridge 2D animal models, cost-effective, scalable, ethical alternative for preclinical research. As field advances, poised play pivotal role understanding biology accelerating development effective anticancer therapies. review article highlights progress most common scaffold-based culturing techniques, pertinent literature on applications ongoing challenges. Graphical

Language: Английский

Citations

64
Emerging technologies for quality control of cell-based, advanced therapy medicinal products DOI Creative Commons

Silvia Zia,

Valeria Pizzuti, Francesca Paris

et al.

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2024, Volume and Issue: 246, P. 116182 - 116182

Published: April 29, 2024

Advanced therapy medicinal products (ATMP) are complex medicines based on gene therapy, somatic cell and tissue engineering. These rapidly arising as novel promising therapies for a wide range of different clinical applications. The process the development well-established ATMPs is challenging. Many issues must be considered from raw material, manufacturing, safety, pricing to assure quality their implementation innovative therapeutic tools. Among ATMPs, cell-based drugs altogether. As standard drugs, technologies control, non-invasive isolation production then needed ensure expanding applications ameliorate safety standardization production. In this review, emerging approaches control described. new techniques, microfluid-based systems show advantages related miniaturization, easy in analytical automation which allow final product.

Language: Английский

Citations

6
Mimicking the Complexity of Solid Tumors: How Spheroids Could Advance Cancer Preclinical Transformative Approaches DOI Open Access

Sylvia Mangani,

Spyros Kremmydas,

Nikos K. Karamanos

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1161 - 1161

Published: March 30, 2025

Traditional 2D cell culture models present significant limitations in replicating the intricate architecture and microenvironment of vivo solid tumors, which are essential for accurately studying cancer initiation, growth, progression, metastasis. This underscores need development advanced preclinical to accelerate research outcomes. Emerging 3D systems, particularly spheroid models, provide a more realistic representation tumor properties by capturing complex interactions occurring within microenvironment, including extracellular matrix dynamics that influence progression. Among breast remains most frequently diagnosed among women globally leading cause cancer-related mortality. Here we emphasize value cell-derived spheroids revealing differential molecular characteristics understanding during early stages invasion into adjacent tissues. Conclusively, this study urgent adopt platforms, given their contributions pharmaceutical targeting. may well offer transformative approach studies enhance our ability test therapeutic efficiency conditions closely mimic growth progression tumors.

Language: Английский

Citations

0
Expression of Basement Membrane Molecules by Wharton Jelly Stem Cells (WJSC) in Full-Term Human Umbilical Cords, Cell Cultures and Microtissues DOI Creative Commons
David Sánchez‐Porras, Daniel Durand‐Herrera,

Ramón Carmona

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 629 - 629

Published: Feb. 15, 2023

Wharton’s jelly stem cells (WJSC) from the human umbilical cord (UC) are one of most promising mesenchymal (MSC) in tissue engineering (TE) and advanced therapies. The cell niche is a key element for both, MSC fully differentiated tissues, to preserve their unique features. basement membrane (BM) an essential structure during embryonic development adult tissues. Epithelial BMs well-known, but similar structures present other histological structures, such as peripheral nerve fibers, myocytes or chondrocytes. Previous studies suggest expression some BM molecules within Jelly (WJ) UC, distribution pattern full profile these have not been yet elucidated. In this sense, aim study was evaluate main WJ, cultured WJSC microtissue (WJSC-MT) formation process. Results confirmed presence pericellular matrix composed by molecules—collagens (IV, VII), HSPG2, agrin, laminin nidogen—around UC. Additionally, ex vivo demonstrated synthesis molecules, except especially WJSC-MT capability synthesize could offer new alternatives generation biomimetic-engineered substitutes where particularly needed.

Language: Английский

Citations

5
Adipose Stromal Cell Spheroids for Cartilage Repair: A Promising Tool for Unveiling the Critical Maturation Point DOI Creative Commons
Azzurra Sargenti,

Simone Pasqua,

Marco Leu

et al.

Bioengineering, Journal Year: 2023, Volume and Issue: 10(10), P. 1182 - 1182

Published: Oct. 12, 2023

Articular cartilage lacks intrinsic regenerative capabilities, and the current treatments fail to regenerate damaged tissue lead only temporary pain relief. These limitations have prompted development of engineering approaches, including 3D culture systems. Thanks their properties capacity recapitulate embryonic processes, spheroids obtained from mesenchymal stromal cells are increasingly studied as building blocks obtain functional tissues. The aim this study was investigate adipose assemble in differentiate toward chondrogenic lineage perspective repair. Spheroids were generated by two different methods (3D chips vs. Ultra-Low Attachment plates), differentiated towards lineage, investigated using molecular biology analyses, biophysical measurement mass density, weight, size spheroids, confocal imaging. Overall, showed ability expressing specific cartilaginous markers that correlate with defining a critical point at which they start mature. Considering spheroid generation method, pilot suggested promising tool for organoids could be used preclinical/clinical personalized therapy.

Language: Английский

Citations

4
Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma DOI Creative Commons

Félix Royo,

Clara Garcia‐Vallicrosa,

Maria Azparren‐Angulo

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(6), P. 1200 - 1200

Published: May 28, 2024

Background: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. Methods: Primary hepatocytes were seeded ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, proliferation, apoptosis analyzed using histological staining techniques. In addition, extracellular vesicles isolated from conditioned media by differential ultracentrifugation. Spheroids exposed cytotoxic drugs, both spheroid growth death measured microscopic imaging flow cytometry vital staining, respectively. Results: Concerning an active outer layer forms boundary the media, while inner core comprises mass debris. Hepatocyte-formed spheroids release into decrease concentration culture can be observed over time. When co-cultured cells, distinct distribution pattern emerges primary hepatocytes, resulting different conformations. Tumoral was compromised upon antitumoral challenges. Conclusions: Treatment mixed drugs enables characterization effects on determining specificity these types.

Language: Английский

Citations

1
Label-free live characterization of mesenchymal stem cell spheroids by biophysical properties measurement DOI Creative Commons
Pasquale Marrazzo, Azzurra Sargenti, Roberta Costa

et al.

Advances in Biological Regulation, Journal Year: 2024, Volume and Issue: unknown, P. 101052 - 101052

Published: Sept. 1, 2024

Language: Английский

Citations

1
CRIPTO’s multifaceted role in driving aggressive prostate cancer unveiled by in vivo, organoid, and patient data DOI Creative Commons
Elisa Rodrigues Sousa, Simone de Brot, Eugenio Zoni

et al.

Oncogene, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract CRIPTO (or CR-1 or TDGF1) is a protein that plays an active role in tumor initiation and progression. We have confirmed increased expression of associated with clinical prostate-specific antigen (PSA) progression human prostate tissues. Our approach involved gaining insight into the signaling castration-resistant Nkx3.1- expressing cells (CARNs), targets for oncogenic transformation cancer (PCa), by integrating existing Cripto flox/flox CARNs model. The most aggressive stage was modeled using inducible Cre under control Nkx3.1 promoter conferring inactivation driving Pten inactivation, Kras activation, lineage tracing yellow fluorescence (EYFP) upon induction. findings provide evidence selective depletion epithelial vivo reduced invasive phenotype, particularly more advanced stages. Moreover, vitro experiments overexpression demonstrated alterations physical features organoids, which correlated tumorigenic activity. Transcriptomic analyses revealed unique CRIPTO/MYC co-activation signature PSA PCa cohort. Taken together, our data highlights invasiveness progression, carries implications biomarkers targeted therapies.

Language: Английский

Citations

0
Adipose Stromal Cell Spheroids for Cartilage Repair: A Promising Tool for Unveiling the Critical Maturation Point DOI Open Access
Azzurra Sargenti,

Simone Pasqua,

Marco Leu

et al.

Published: Sept. 27, 2023

Articular cartilage lacks intrinsic regenerative capabilities, and the current treatments fail to regenerate damaged tissue lead only temporary pain relief. These limitations have prompted development of engineering approaches, including 3D culture systems. Thanks their properties capacity recapitulate embryonic processes, spheroids obtained from mesenchymal stromal cells are increasingly studied as building blocks obtain functional tissues. The aim this study was investigate adipose assemble in differentiate toward chondrogenic lineage perspective repair. Spheroids were generated by two different methods (3D chips vs Ultra-Low Attachment plates), differentiated lineage, investigated by: molecular biology analyses, biophysical measurement mass density, weight, size spheroids, confocal imaging. Overall, showed ability expressing specific cartilaginous markers that correlate with defining a critical point at which they start mature. Considering spheroid generation method, pilot suggested promising tool for organoids could be used preclinical/clinical realization personalized therapy.

Language: Английский

Citations

1
Review on new approach methods to gain insight into the feto-maternal interface physiology DOI Creative Commons
Ramkumar Menon, Louis J. Muglia,

Lisa Hara Levin

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 30, 2023

Non-human animals represent a large and important feature in the history of biomedical research. The validity their use, terms reproducible outcomes translational confidence to human situation, as well ethical concerns surrounding that have been remain controversial topics. Over last 10 years, communities developing microphysiological systems (MPS) produced new approach method (NAMs) such organoids organs-on-a-chip. These alternative methodologies shown indications greater reliability translatability than animal use some areas, more humane substitutions for these settings, - with continued scientific effort may change conduct basic research, clinical studies, safety testing, drug development. Here, we present an introduction human-relevant suggest how suite pregnancy associated feto-maternal interface system-oriented NAMs be integrated reliable partial-/full replacements investigators, significantly aid animal-/environmental welfare, improve healthcare outcomes.

Language: Английский

Citations

1