Considerations in the development of pluripotent stem cell–based therapies DOI

Justine J. Cunningham,

Alexandra Capela,

Catherine Priest

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 399 - 449

Published: Nov. 29, 2024

Language: Английский

Organoids are not organs: Sources of variation and misinformation in organoid biology DOI Creative Commons
Kim B. Jensen, Melissa H. Little

Stem Cell Reports, Journal Year: 2023, Volume and Issue: 18(6), P. 1255 - 1270

Published: June 1, 2023

In the past decade, term organoid has moved from obscurity to common use describe a 3D in vitro cellular model of tissue that recapitulates structural and functional elements vivo organ it models. The is now applied structures formed as result two distinct processes: capacity for adult epithelial stem cells re-create niche ability direct differentiation pluripotent self-organizing multicellular organogenesis. While these fields rely upon different cell types recapitulate processes, both share challenges around robustness, accuracy, reproducibility. Critically, organoids are not organs. This commentary serves discuss challenges, how they impact genuine utility, shine light on need improve standards all approaches.

Language: Английский

Citations

47

Stem cell-derived intestinal organoids: a novel modality for IBD DOI Creative Commons

Cheng‐mei Tian,

Meifeng Yang, Haoming Xu

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 21, 2023

Abstract The organoids represent one of the greatest revolutions in biomedical field past decade. This three-dimensional (3D) micro-organ cultured vitro has a structure highly similar to that tissue and organ. Using regeneration ability stem cells, 3D organ-like called intestinal is established, which can mimic characteristics real organs, including morphology, function, personalized response specific stimuli. Here, we discuss current cell-based models, understanding molecular pathophysiology, high-throughput screening drugs, drug efficacy testing, toxicological evaluation, organ-based inflammatory bowel disease (IBD). We summarize advances limitations state-of-the-art reconstruction platforms for organoids. challenges, advantages, prospects organs as an model system precision medicine are also discussed.

Language: Английский

Citations

28

Breast cancer organoids derived from patients: A platform for tailored drug screening DOI Creative Commons
Yen‐Dun Tony Tzeng,

Jui‐Hu Hsiao,

Ling‐Ming Tseng

et al.

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 217, P. 115803 - 115803

Published: Sept. 12, 2023

Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor pathology development novel therapeutics are pivotal for advancing breast treatment. Contemporary investigation heavily leans on in vivo models conventional cell culture techniques. Nonetheless, these approaches often encounter high failure rates clinical trials due to species disparities tissue structure variations. To address this, three-dimensional cultivation organoids, resembling organ-like structures, has emerged promising alternative. Organoids represent innovative vitro that mirror microenvironments. They retain original tumor's diversity facilitate expansion samples from diverse origins, facilitating representation varying stages. Optimized organoid models, under precise conditions, offer benefits including convenient sample acquisition, abbreviated durations, genetic stability. These attributes ensure faithful replication traits cells. As intricate cellular entities boasting spatial arrangements, harbor potential precision medicine, organ transplantation, modeling diseases, gene therapy, drug innovation. This review delivers an overview techniques outlines future prospects modeling.

Language: Английский

Citations

14

The Evolution of Technology‐Driven In Vitro Models for Neurodegenerative Diseases DOI Creative Commons
Eleonora De Vitis,

Antonella Stanzione,

Alessandro Romano

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 17, 2024

Abstract The alteration in the neural circuits of both central and peripheral nervous systems is closely related to onset neurodegenerative disorders (NDDs). Despite significant research efforts, knowledge regarding NDD pathological processes, development efficacious drugs are still limited due inability access reproduce components system its intricate microenvironment. 2D culture too simplistic accurately represent more complex dynamic situation cells vivo have therefore been surpassed by 3D systems. However, models suffer from various limitations that can be overcome employing two innovative technologies: organ‐on‐chip printing. In this review, an overview advantages shortcomings microfluidic platforms extracellular matrix‐like biomaterials will given. Then, combination microfluidics hydrogels as a new synergistic approach study analyzing latest advances brain‐on‐chip for explored.

Language: Английский

Citations

6

Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance DOI Open Access
Samuele Tardito,

Serena Matis,

Maria Raffaella Zocchi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7131 - 7131

Published: June 28, 2024

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Therefore, need for new therapeutic strategies still a challenge. Surgery and chemotherapy represent first-line interventions; nevertheless, prognosis metastatic CRC (mCRC) patients remains unacceptable. An important step towards targeted therapy came from inhibition epidermal growth factor receptor (EGFR) pathway, by anti-EGFR antibody, Cetuximab, or specific tyrosine kinase inhibitors (TKI). mouse-human chimeric monoclonal antibody (mAb), binds to extracellular domain EGFR thus impairing EGFR-mediated signaling reducing cell proliferation. TKI can affect biochemical pathway at different steps along cascade. Apart other mAbs have been developed, such as Panitumumab. Both antibodies approved treatment KRAS-NRAS wild type mCRC, alone in combination with chemotherapy. These display strong differences activating host immune system against CRC, due their immunoglobulin isotypes. Although are efficient, drug resistance occurs high frequency. Resistant tumor populations either already be present before develop later adaptations genomic mutations pathway. Numerous efforts made improve efficacy find agents that able block downstream cascade molecules. Indeed, we examined importance analyzing antibody-drug conjugates (ADC) developed overcome and/or stimulate host's immunity growth. Also, patient-derived organoid cultures useful feasible vitro model study behavior response. Organoids reflect genetic heterogeneity found tissue origin, representing unique tool personalized medicine. Thus, CRC-derived smart studying microenvironment preclinical assay drugs.

Language: Английский

Citations

6

Enhancing Osteoblast Differentiation from Adipose-Derived Stem Cells Using Hydrogels and Photobiomodulation: Overcoming In Vitro Limitations for Osteoporosis Treatment DOI Creative Commons
Daniella Da Silva, Anine Crous, Heidi Abrahamse

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(7), P. 6346 - 6365

Published: June 25, 2024

Osteoporosis represents a widespread and debilitating chronic bone condition that is increasingly prevalent globally. Its hallmark features include reduced density heightened fragility, which significantly elevate the risk of fractures due to decreased presence mature osteoblasts. The limitations current pharmaceutical therapies, often accompanied by severe side effects, have spurred researchers seek alternative strategies. Adipose-derived stem cells (ADSCs) hold considerable promise for tissue repair, albeit they encounter obstacles such as replicative senescence in laboratory conditions. In comparison, employing ADSCs within three-dimensional (3D) environments provides an innovative solution, replicating natural extracellular matrix environment while offering controlled cost-effective vitro platform. Moreover, utilization photobiomodulation (PBM) has emerged method enhance ADSC differentiation proliferation potential instigating cellular stimulation facilitating beneficial performance modifications. This literature review critically examines shortcomings osteoporosis treatments investigates synergies between 3D cell culture PBM augmenting towards osteogenic lineages. primary objective this study assess efficacy combined enhancing management. research notably distinguished its thorough scrutiny existing literature, synthesis recent advancements, identification future trajectories, databases PubMed, Scopus, Web Science, Google Scholar review. Furthermore, exploration biomechanical biophysical stimuli holds refining treatment outlook suggests integrating with housed advancing regeneration efforts. Importantly, aspires catalyse further advancements therapeutic strategies regeneration.

Language: Английский

Citations

5

Advances in the knowledge and therapeutics of schizophrenia, major depression disorder, and bipolar disorder from human brain organoid research DOI Creative Commons
Rosa Villanueva

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: July 12, 2023

Tridimensional cultures of human induced pluripotent cells (iPSCs) experimentally directed to neural differentiation, termed “brain organoids” are now employed as an in vitro assay that recapitulates early developmental stages nervous tissue differentiation. Technical progress culture methodology enabled the generation regionally specialized organoids with structural and neurochemical characters distinct encephalic regions. The technical process organoid elaboration is undergoing progressively implementation, but current robustness has attracted attention psychiatric research substitute/complement animal experimentation for analyzing pathophysiology disorders. Numerous morphological, structural, molecular functional insights disorders have been uncovered by comparing brain made iPSCs obtained from control healthy subjects patients. Brain were also response conventional treatments, search new drugs, anticipate therapeutic individual patients a personalized manner. In this review, we gather data studying cerebral three most frequent serious disorders: schizophrenia, major depression disorder, bipolar disorder. Among these studies, emphasize: (i) origin pathologies takes place embryonic development; (ii) existence shared pathogenic aspects among disorders; (iii) occurrence differences between bearing same (iv) alterations can be activated or aggravated environmental signals genetic risk

Language: Английский

Citations

11

Enhanced mitochondrial function and delivery from adipose-derived stem cell spheres via the EZH2-H3K27me3-PPARγ pathway for advanced therapy DOI Creative Commons
Ming‐Min Chang, Dinh‐Toi Chu,

Sheng-Che Lin

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 11, 2025

Abstract Background Microenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy cell function. However, specific roles of histone modifications mitochondrial dynamics human adipose-derived cells (ASCs) during morphological transformations remain poorly understood. In this study, we aim to elucidate mechanisms by which ASC sphere formation enhances function, delivery, rescue efficiency. Methods ASCs were cultured on chitosan nano-deposited surfaces form 3D spheres. Mitochondrial activity ATP production assessed using MitoTracker staining, Seahorse XF analysis, luminescence assays. Single-cell RNA sequencing, followed Ingenuity Pathway Analysis (IPA), was conducted uncover key regulatory pathways, validated through molecular techniques. involvement confirmed inhibitors or PPARγ-modulating drugs. structural integrity delivery efficiency evaluated after isolation. Results Chitosan-induced spheres exhibited unique compact morphology, characterized condensed cristae, enhanced activity, increased oxidative phosphorylation. High expressions complex I genes elevated levels proteins observed without an increase reactive oxygen species (ROS). Epigenetic modification H3K27me3 PPARγ discovered inhibiting with EZH2 inhibitor GSK126 adding agonist Rosiglitazone (RSG). Isolated mitochondria from showed improved stability efficiency, suppressed inflammatory cytokines LPS- TNFα-induced inflamed cells, rescued damage, thereby enhancing function promoting recovery. Conclusion Enhancing via EZH2-H3K27me3-PPARγ pathway offers alternative strategy conventional cell-based therapies. High-functional show potential medicine applications.

Language: Английский

Citations

0

Exploring human brain development and disease using assembloids DOI
Sih‐Rong Wu, Tomasz J. Nowakowski

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

From gut to liver: organoids as platforms for next-generation toxicology assessment vehicles for xenobiotics DOI Creative Commons
Sulaiman Mohammed Alnasser

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 26, 2025

Traditional toxicological assessment relied heavily on 2D cell cultures and animal models of study, which were inadequate for the precise prediction human response to chemicals. Researchers have now shifted focus organoids assessment. Organoids are 3D structures produced from stem cells that mimic shape functionality organs a number advantages compared traditional study. They capacity replicate intricate cellular microenvironment in vivo interactions. offer physiologically pertinent platform is useful researchers monitor responses more realistic manner evaluate drug toxicity. Additionally, can be created unique patient, allowing individualized research providing understanding inter-individual heterogeneity responses. Recent developments use gut liver xenobiotics (environmental toxins drugs) reviewed this article. Gut reveal potential damage digestive system how affect nutrient absorption barrier function. Liver primary site detoxification metabolism xenobiotics, usually routed gut. Hence, these linked crucial evaluating chemical or pollutant induced organ toxicity, forecasting their pharmacokinetics. When incorporated into development process, organoid improve accuracy efficiency safety assessments, leading safer effective treatments. We also discuss limitations using organoid-based assays, future prospects, including need standardized protocols overcoming reproducibility issues.

Language: Английский

Citations

0