Stem Cell Reviews and Reports最新文献

The interplay between metabolic signaling and stem cell biology has gained increasing attention, though the underlying molecular mechanisms remain incompletely elucidated. In this study, we identify and characterize the role of adapalene (ADA), a retinoic acid receptor (RAR) agonist, in modulating the migration behavior of hematopoietic stem cells (HSCs). Our initial findings reveal that ADA treatment suppresses hematopoietic stem and progenitor cell (HSPC) mobilization induced by AMD3100 and G-CSF. Furthermore, we demonstrate that ADA treatment upregulates the surface expression of CXCR4 on HSPCs, resulting in enhanced chemotaxis towards CXCL12. Mechanistically, our study suggests that ADA enhances CXCR4 surface presentation without increasing CXCR4 mRNA levels, pointing towards a non-canonical role of RAR signaling in regulating intracellular trafficking of CXCR4. In vivo experiments show that ADA administration significantly enhances HSC homing efficiency. Additionally, competitive transplantation assays indicate a marked increase in donor chimerism following ADA treatment. These findings highlight the critical role of retinoic acid signaling in regulating HSC homing and suggest its potential for advancing novel HSC-based therapeutic strategies.

Corneal limbal epithelial stem cells (LESCs) play a crucial role in corneal epithelium regeneration. Severe damage to these cells can result in limbal stem cell deficiency (LSCD), characterized by repeated corneal conjunctivalization, leading to corneal turbidity and scar formation. Restoring functional LESCs and their ecological location are essential for treating LSCD. The goal of this review is to provide researchers and clinicians with key insights into LESCs biology and to conclude the current cell-based therapies advancement in LSCD treatments. Therapeutic cell resources mainly include mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), skin keratinocyte stem cells (SKCs), and oral mucosal epithelial cells (OMECs).

Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids.

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is recognized as a major contributor to cancer-related mortality worldwide. Cancer stem cells (CSCs) are a tiny group of cancer cells that possess a significant ability to regenerate themselves, form tumors, and undergo differentiation. CSCs have a pivotal role in the initiation, spread, recurrence, and resistance to treatment of cancer. As a result, they are very susceptible to being targeted for therapeutic intervention. The potential to cure HCC may be achieved by efficiently targeting drugs that eradicate cancer stem cells. Mitochondria have a crucial function in granting drug resistance to cancer stem cells by means of mitochondrial metabolism, biogenesis, and dynamics. Dysfunction in mitochondrial metabolic processes, such as mitochondrial oxidative phosphorylation (OXPHOS), calcium signaling, and reactive oxygen species (ROS) generation, contributes to the initiation and progression of human malignancies, including HCC. ROS have both beneficial and detrimental effects depending on their concentration. Consequently, ROS have become a prominent subject in the study of the fundamental mechanisms of HCC. Furthermore, an imbalance in the process of creating new mitochondria is a characteristic feature of CSCs, and an increase in mitochondrial biogenesis is associated with the heightened resistance observed in CSCs. This article provides a detailed examination of the involvement of mitochondria in the preservation of CSCs, as well as the spread of HCC. A deeper understanding of how mitochondria participate in tumorigenesis and drug resistance could result in the discovery of novel cancer treatments.

Background: Currently, most inherited retinal diseases lack curative interventions, and available treatment modalities are constrained to symptomatic approaches. Retinal organoid technology has emerged as a method for treating inherited retinal diseases, with growing academic interest in recent years. The purpose of this review was to systematically organize the current protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal disease and to investigate the application of retinal organoids in inherited retinal disease research.

Methods: Data were collected from the PubMed, Scopus, and Web of Science databases using a keyword search. The main search term used was "retinal organoid," accompanied by secondary keywords such as "optic cup," "three-dimensional," and "self-organizing." The final search was conducted on October 2, 2024.

Results: Of the 2,129 studies retrieved, 130 were included in the qualitative synthesis. The protocols for the generation of retinal organoids in inherited retinal disease research use five major approaches, categorized into 3D and a combination of 2D/3D approaches, implemented with modifications. Disease phenotypes have been successfully reproduced via the generation of retinal organoids from the induced pluripotent stem cells of individuals with inherited retinal diseases, facilitating the progression of research into novel therapeutic developments. Cells have been obtained from retinal organoids for cell therapy, and progress toward their potential integration into clinical practice is underway. Considering their potential applications, retinal organoid technology has shown promise across various domains.

Conclusion: In this systematic review, we organized protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal diseases. Retinal organoid technology has various applications including disease modeling, screening for novel therapies, and cell replacement therapy. Further advancements would make this technology a clinically significant tool for patients with inherited retinal diseases.

Induced pluripotent stem cells (iPSCs) have emerged as promising in vitro tools, providing a robust system for disease modelling and facilitating drug screening. Human iPSCs have been successfully differentiated into lung cells and three-dimensional lung spheroids or organoids. The lung is a multicellular complex organ that develops under the symphonic influence of the microenvironment. Here, we hypothesize that the generation of lung organoids in a controlled microenvironment (cmO) (oxygen and pressure) yields multicellular organoids with architectural complexity resembling the lung alveoli. iPSCs were differentiated into mature lung organoids following a stepwise protocol in an oxygen and pressure-controlled microenvironment. The organoids developed in the controlled microenvironment displayed complex alveolar architecture and stained for SFTPC, PDPN, and KRT5, indicating the presence of alveolar epithelial type II and type I cells, as well as basal cells. Moreover, gene and protein expression levels were also increased in the cmO. Furthermore, pathway analysis of proteomics revealed upregulation of lung development-specific pathways in the cmO compared to those growing in normal culture conditions. In summary, by using a controlled microenvironment, we established a complex multicellular lung organoid derived from iPSCs as a novel cellular model to study lung alveolar biology in both lung health and disease.

The discipline of 3D cell modeling is currently undergoing a surge of captivating developments that are enhancing the realism and utility of tissue simulations. Using bioinks which represent cells, scaffolds, and growth factors scientists can construct intricate tissue architectures layer by layer using innovations like 3D bioprinting. Drug testing can be accelerated and organ functions more precisely replicated owing to the precise control that microfluidic technologies and organ-on-chip devices offer over the cellular environment. Tissue engineering is becoming more dynamic with materials that can modify their surroundings with the advent of hydrogels and smart biomaterials. Advances in spheroids and organoids are not only bringing us towards more effective and customized therapies, but they are also improving their ability to resemble actual human tissues. Confocal and two-photon microscopy are examples of advanced imaging methods that provide precise images of the functioning and interaction of cells. Artificial Intelligence models have applications for enhanced scaffold designs and for predicting the response of tissues to medications. Furthermore, via strengthening predictive models, optimizing data analysis, and simplifying 3D cell culture design, artificial intelligence is revolutionizing this field. When combined, these technologies are improving our ability to conduct research and moving us toward more individualized and effective medical interventions.