Stem Cell Reviews and Reports最新文献

{"title":"Adapted Exosomes for Addressing Chemotherapy-induced Premature Ovarian Insufficiency.","authors":"Mohammad Mousaei Ghasroldasht, Hang-Soo Park, Farzana Liakath Ali, Analea Beckman, Mahya Mohammadi, Nina Hafner, Ayman Al-Hendy","doi":"10.1007/s12015-024-10820-5","DOIUrl":"10.1007/s12015-024-10820-5","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI.</p><p><strong>Methods: </strong>Adapted exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs) under a specific co-culture system and used for treating in vitro and in vivo models of chemotherapy-induced premature ovarian insufficiency.</p><p><strong>Results: </strong>In vitro models revealed the significant impact of adapted exosomes, which promoted granulosa cell proliferation, decrease apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model indicated the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and adapted exosome-treated groups. Notably, the adapted exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. MiRNA profiling revealed distinctive cargo in the adapted exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with adapted exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway-a crucial mechanism in mitigating chemotherapy-induced POI.</p><p><strong>Conclusions: </strong>This study introduces an exosome-based therapeutic approach, emphasizing the importance of exosome cargo composition in treating disorders. Further investigation into the identified miRNA profile in adapted exosomes is necessary to clarify the underlying mechanisms, potentially leading to the development of a new treatment for clinical premature ovarian insufficiency.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"779-796"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Applications of Organoids in Gynecological Diseases.","authors":"Jian Yang, Wenwen Li, Zihan Zhang, Zhonglei Xu, Wenjing Zhu, Jing Wang, Wenyan Wang","doi":"10.1007/s12015-024-10833-0","DOIUrl":"10.1007/s12015-024-10833-0","url":null,"abstract":"<p><p>Organoids are rapidly self-organizing 3D in vitro cultures derived from pluripotent stem cells (PSCs) or adult stem cells (ASCs) that possess disease-like characteristics with high success rates. Due to their ability to retain tissue structure, biological phenotypes, and genetic information, they have been utilized as a novel in vitro model for disease research. In recent years, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, ovaries, and cervix by culturing stem cells with cytokines in 3D scaffolds. The integration of organoids with animal models, organ-on-a-chip systems, and 3D printing technologies offers a novel preclinical model for exploring disease mechanisms and developing treatments. This review elaborate on the recent research progress of stem cells-formed organoids in the field of gynecology from the aspects of constructing gynecological disease organoids, drug screening and new drug development, simulation modeling, allogeneic transplantation, regenerative medicine and personalized treatment.\"</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"629-644"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening.","authors":"Martina Servetti, Martino Caramia, Giulia Parodi, Fabrizio Loiacono, Ennio Nano, Giorgia Biddau, Lorenzo Ferrando, Lisastella Morinelli, Pierluigi Valente, Sergio Martinoia, Andrea Escelsior, Gianluca Serafini, Serena Tamburro, Simona Baldassari, Anna Fassio, Fabio Benfenati, Anna Corradi, Bruno Sterlini","doi":"10.1007/s12015-025-10845-4","DOIUrl":"10.1007/s12015-025-10845-4","url":null,"abstract":"<p><p>Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings. This study focuses on standardizing and optimizing the procedure for iPSC-derived glutamatergic neurons generation through the inducible overexpression of Neurogenin-2. Noteworthy refinements include stringent scrutiny of genomic rearrangements post-fibroblast reprogramming, selection of a homogeneously integrated NGN2-cassettes population, and the incorporation of an intermediate step during neuronal differentiation to store neuronal progenitors. The neural culture showed a high degree of neuronal maturation and consistency, as shown by single-cell and network electrophysiological recordings. These advancements aim to provide more reliable tools for disease modelling and drug screening in neurological disorders.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"816-833"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevating Dermatology Beyond Aesthetics: Perinatal-Derived Advancements for Rejuvenation, Alopecia Strategies, Scar Therapies, and Progressive Wound Healing.","authors":"Mohammad Amin Khalilzad, Javad Mohammadi, Soumayeh Amirsaadat, Sajad Najafi, Sona Zare, Mohammad Ali Nilforoushzadeh, Mitra Khalilzad, Ayoub Khaghani, Mohammad Reza Fayyazi Soltankouhi, Alireza Hajimohammad","doi":"10.1007/s12015-024-10835-y","DOIUrl":"10.1007/s12015-024-10835-y","url":null,"abstract":"<p><p>Dermatologists have been interested in recent advancements in regenerative therapy. Current research is actively investigating the possibility of placental tissue derivatives to decelerate the skin aging process, enhance skin regeneration, reduce scarring, and prevent hair loss. Amniotic membranes (AM) play a crucial role in regenerative medicine as they serve as a suitable means of transporting stem cells, growth hormones, cytokines, and other essential compounds. Regulating an intricate network of biological processes improves the development and repair of tissues. Studies done by dermatologists indicate that several compounds found in the decidua, umbilical cord, and amniotic membrane have the potential to be used for regeneration. Examples include mesenchymal stem cells, growth factors, and immunomodulatory pharmaceuticals. Due to research and technological developments, scientists may use placental sections to facilitate skin regeneration, minimize scarring, and expedite wound healing. This study examines the current state of dermatological therapy, with a focus on using derivatives obtained from fetal tissue as the basis. The critical areas of study focus on this strategy are the potential benefits, growth opportunities, and recovery rates. Based on a thorough examination of the available literature and clinical data, we want to make definitive conclusions on the possible influence of fetal tissue derivatives in dermatological therapy.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"709-729"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria Express Functional Signaling Ligand-Binding Receptors that Regulate their Biological Responses - the Novel Role of Mitochondria as Stress-Response Sentinels.","authors":"Katarzyna Brzezniakiewicz-Janus, Justyna Jarczak, Adrian Konopko, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak","doi":"10.1007/s12015-025-10847-2","DOIUrl":"10.1007/s12015-025-10847-2","url":null,"abstract":"<p><p>Evidence accumulated mitochondria, as the \"powerplants of the cell,\" express several functional receptors for external ligands that modify their function and regulate cell biology. This review sheds new light on the role of these organelles in sensing external stimuli to facilitate energy production for cellular needs. This is possible because mitochondria express some receptors on their membranes that are responsible for their autonomous responses. This is not surprising given the widely accepted hypothesis that these intracellular organelles originated from prokaryotic ancestors that fused with eukaryotic cells during early evolution. It has been reported that mitochondria express functional estrogen, androgen, glucocorticoid, 5-hydroxytryptamine, melatonin, and cannabinoid receptors. What is intriguing is recent evidence showing that mitochondria could also be directly regulated by active mediators of intracellular complement (complosome) and intrinsic mediators of purinergic signaling. Accordingly, they express receptors for intracellular complement cleavage fragments (C5a and C3a) as well as for adenosine triphosphate (ATP), which, besides its crucial role in transferring energy in the cells, is also an important signaling molecule interacting with P2X7 receptor expressed not only on the cell surface but also on the mitochondria membrane. Based on this, intrinsic complosome and purinergic signaling mediators emerge as important cooperating regulators of reactive oxygen species (ROS) release from mitochondria and activators of intracellular pattern recognition receptor Nlrp3 inflammasome. This activation within the beneficial \"hormetic zone response\" regulates cell metabolism, proliferation, migration, and adaptation to the surrounding challenges of the microenvironment in a favorable way.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"597-604"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.","authors":"Georgia P Wong, Sunhild Hartmann, Olivia Nonn, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Natasha de Alwis, Ciara N Murphy, Natasha Pritchard, Ralf Dechend, Natalie J Hannan, Stephen Tong, David G Simmons, Tu'uhevaha J Kaitu'u-Lino","doi":"10.1007/s12015-024-10831-2","DOIUrl":"10.1007/s12015-024-10831-2","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist. We characterised LGR5/LGR4, their ligands/targets in human placenta, with further assessments on dysregulation in preeclampsia/fetal growth restriction (FGR). LGR5 mRNA was unaltered in first trimester (n = 11), preterm (n = 9) and term (n = 11) placental lysate. LGR5 was enriched in human trophoblast stem cells (hTSCs) and downregulated with differentiation to extravillous trophoblasts (p < 0.0215) and syncytiotrophoblasts (p < 0.0350). In situ hybridisation localised LGR5 to unique, proliferative MKI67 + mononuclear trophoblasts underlying syncytium which concurred with proposed progenitor identities in single-cell transcriptomics. LGR5 expression was significantly reduced in placentas from early-onset preeclampsia (p < 0.0001, n = 81 versus n = 19 controls), late-onset preeclampsia (p = 0.0046, n = 20 versus n = 33 controls) and FGR (p = 0.0031, n = 34 versus n = 17 controls). LGR4 was elevated in first trimester versus preterm and term placentas (p = 0.0412), in placentas with early-onset preeclampsia (p = 0.0148) and in FGR (p = 0.0417). Transcriptomic analysis and in vitro hTSC differentiation to both trophoblast lineages suggested LGR4 increases with differentiation. Single-nucleus RNA sequencing of placental villous samples supported LGR5 and LGR4 localisation findings. Hypoxia/proinflammatory cytokine treatment modelling elements experienced by the placenta in placental insufficiency pathogenesis did not significantly alter LGR5/LGR4. Ligands R-spondins 1/3/4, and neutralising targets ring finger protein 43 (RNF43) and zinc and ring finger 3 (ZNRF3) were also reduced in placentas from preeclamptic pregnancies. This study is the first to describe LGR5/LGR4 and their signalling partner expression in human placenta. Their dysregulations in the preeclamptic placenta allude to disruptions to integral trophoblast stem cell function/differentiation that may occur during placental development related to WNT signalling.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"872-896"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revitalizing Vision: Eye Drops and Corneal Limbal Stem Cells Survival.","authors":"Yahui Wang, Mojdeh Yousefi, Mohammad Reza Ghasemzadeh Fard, Nasrin Masihpour, Payam Ali Khiavi, Khadije Yousefi, Maryam Hajizadeh, Sepideh KarkonShayan","doi":"10.1007/s12015-025-10841-8","DOIUrl":"10.1007/s12015-025-10841-8","url":null,"abstract":"<p><p>In the quest to transform vision care, researchers have been investigating novel methods to boost the efficacy of eye drops and enhance the survival of corneal limbal stem cells. Aimed at rejuvenating vision, these innovations seek to tackle a range of ocular conditions and restore sight to those in need. This article examines the most recent advancements in eye drops and corneal limbal stem cells, highlighting their potential to revolutionize ophthalmology. Findings from various studies indicate that the drive to rejuvenate vision has resulted in significant progress within the field of ophthalmology, especially regarding eye drops and corneal limbal stem cells. By improving the effectiveness of eye drops and increasing the survival rates of CLSCs, researchers are creating pathways for more sustainable and effective treatment options. These advancements offer great hope for patients experiencing various ocular issues, suggesting a future where vision restoration is attainable. As research continues to refine these strategies, we can look forward to an era marked by better visual outcomes and an enhanced quality of life for many individuals around the world.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"730-743"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Characterisation of Bone Marrow-Derived Haematopoietic Stem/Progenitor Cells from HIV-Infected Individuals.","authors":"Priyal Mistry, Joachim J C Potgieter, Michael S Pepper, Chrisna Durandt","doi":"10.1007/s12015-024-10834-z","DOIUrl":"10.1007/s12015-024-10834-z","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"900-903"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking a Decade of Research on Embryo-Derived Extracellular Vesicles: Discoveries Made and Paths Ahead.","authors":"Islam M Saadeldin, Krishna Chaitanya Pavani, Juri Gnagnarelli, Seif Ehab, Abdullah M Assiri, Ann Van Soom","doi":"10.1007/s12015-025-10844-5","DOIUrl":"10.1007/s12015-025-10844-5","url":null,"abstract":"<p><p>Over the past decade, research on embryo-derived extracellular vesicles (EVs) has unveiled their critical roles in embryonic development and intercellular communication. EVs secreted by embryos are nanoscale lipid bilayer vesicles that carry bioactive cargo, including proteins, lipids, RNAs, and DNAs, reflecting the physiological state of the source cells. These vesicles facilitate paracrine and autocrine signaling, influencing key processes such as cell differentiation, embryo viability, and endometrial receptivity. Studies reveal that EVs can traverse the zona pellucida, transferring molecular signals that enhance blastocyst formation and support embryo-maternal crosstalk. EVs have emerged as non-invasive biomarkers for embryo quality, with their cargo providing insights into genetic integrity and developmental competence. Advances in isolation and characterization techniques have identified specific microRNA (miRNAs) and transcription factors within EVs, offering potential for use in preimplantation genetic screening (PGS) and sex determination. Moreover, EV-mediated interactions with the maternal environment are critical for successful implantation, as they modulate gene expression and immune responses in endometrial and oviductal cells. Despite these advancements, challenges persist, including the standardization of EV isolation methods and the low yield of EVs DNA from spent culture media. Future research should aim to refine analytical techniques, explore EV-miRNA profiling, and investigate the mechanisms underlying EV-mediated signaling. By addressing these gaps, EVs could revolutionize embryo selection and reproductive technologies, offering new strategies to improve outcomes in assisted reproduction and animal breeding.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"698-708"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXL4-Related Mitochondrial Depletion Syndrome Underscores the role of Mitophagy in Stem Cell Differentiation during Embryogenesis.","authors":"Pankaj Prasun","doi":"10.1007/s12015-025-10854-3","DOIUrl":"10.1007/s12015-025-10854-3","url":null,"abstract":"<p><p>FBXL4- related mitochondrial depletion syndrome is a very rare inherited disorder characterized by global developmental delays, hypotonia, seizures, growth failure, and early onset lactic acidosis. Often, it is associated with structural brain and heart defects, and facial dysmorphism suggesting an embryogenesis defect. FBXL4 encodes F-box and leucine-rich repeat protein 4 (FBXL4) which is involved in mitochondrial quality control and maintenance by regulating mitophagy. A recent study suggests that FBXL4 deficiency leads to increased mitophagy. Fine tuning of mitophagy is essential for stem cell differentiation during embryogenesis. The disruption of this process is the likely explanation of developmental defects in FBXL4- related mitochondrial depletion syndrome.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"897-899"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}