{"title":"Precision Reprogramming-Restoring Function to Aged Cells.","authors":"Arjun Jain, Yuuki Hosokawa, Kevin Joseph","doi":"10.1089/cell.2025.0018","DOIUrl":"https://doi.org/10.1089/cell.2025.0018","url":null,"abstract":"<p><p>Sahu et al. (2024) demonstrate that targeted partial reprogramming with Oct4, Sox2, and Klf4 (OSK) delivered via adeno-associated virus (AAV) to Cdkn2a-positive cells rejuvenates senescent cells while maintaining cellular identity. In a progeroid and naturally aged mouse model, a single AAV injection improved lifespan, reduced inflammation, restored tissue integrity, and enhanced wound healing. Complementary results in human fibroblasts confirmed Cdkn2a-driven OSK expression attenuated inflammation-associated genes during replicative senescence and treatments inducing DNA damage. These encouraging results highlight its potential as a safer alternative to systemic senolytic therapies for age-associated disorders.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reprogramming of Different Cell Lineages into Functional β-Cell Substitutes.","authors":"Anna A Dattoli, Yosip Kelemen, Xiaofeng Huang","doi":"10.1089/cell.2024.0102","DOIUrl":"https://doi.org/10.1089/cell.2024.0102","url":null,"abstract":"<p><p>Since its first use in 1922, insulin therapy has transformed diabetes from a fatal disease to a manageable condition. However, long-term insulin injections lead to significant complications. β-cell replacement, derived from either a limited number of deceased donors or embryonic stem cells, offers an encouraging alternative. While these procedures allow patients to be insulin-independent, they still require systemic immunosuppressants to prevent graft rejection, which poses immunological challenges. Direct reprogramming holds considerable promise as a method for generating β-cells from various sources, enabling autologous therapies that mitigate the risk of immune rejection and eliminate the need to harvest cells from embryos. This review provides an overview of the latest advances in direct reprogramming strategies, with a focus on key transcriptional regulators that drive phenotypic conversion and maintenance of various cell types into β-like cells.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2025-06-01Epub Date: 2025-04-22DOI: 10.1089/cell.2024.0071
Chao Ma, Yue Yi, Changji Guan
{"title":"Menstrual Blood-Derived Mesenchymal Stem Cells Improve Endometrial Receptivity in a Mouse Model of Embryonic Implantation Dysfunction.","authors":"Chao Ma, Yue Yi, Changji Guan","doi":"10.1089/cell.2024.0071","DOIUrl":"10.1089/cell.2024.0071","url":null,"abstract":"<p><p>The decrease of endometrial receptivity leads to repeated implantation failure (RIF) during in vitro fertilization and embryo transfer. To explore the therapeutic potential of menstrual blood-derived mesenchymal stem cells (MenSCs) in addressing RIF, we established a murine model of embryonic implantation dysfunction using mifepristone. Subsequently, we administered MenSCs to these mice via tail vein injection and assessed their impact on the implantation and pregnancy rates of the affected mice. Furthermore, we conducted immunohistochemical staining on uterine tissues from these mice to examine the expression of endometrial receptivity markers, specifically vascular endothelial growth factor (VEGF)-A, HAND2, and HOXA10 following MenSCs transplantation. In parallel, we conducted in vitro studies to elucidate the molecular mechanisms of cell therapy by measuring the expression levels of VEGF-A, HAND2, and HOXA10 in endometrial stromal cells using real-time PCR and western blotting. In our mifepristone-induced mouse models, we observed a reduction in both pregnancy rates and implantation sites; however, these parameters were significantly improved after MenSCs transplantation. Similarly, the expression levels of VEGF-A, HAND2, and HOXA10 in the uterine tissues of the mifepristone group were diminished, but these levels were restored following MenSCs therapy. In vitro, after mifepristone treating, the expression of VEGF-A, HAND2, and HOXA10 decreased in endometrial stromal cells, but their expression increased after MenSCs coculture supernatant. In conclusion, these results demonstrated that MenSCs transplantation could increase endometrial receptivity by upregulating VEGF-A, HAND2, and HOXA10 expression. This study suggests MenSCs as a novel stem cell candidate in the treatment of RIF.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"124-133"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2025-06-01Epub Date: 2025-03-26DOI: 10.1089/cell.2025.0013
Seung-Won Lee, Jungsun Kim
{"title":"Locking the Fate: How PROX1 Represses Plasticity and Liver Cancer.","authors":"Seung-Won Lee, Jungsun Kim","doi":"10.1089/cell.2025.0013","DOIUrl":"10.1089/cell.2025.0013","url":null,"abstract":"<p><p>A Transcriptional Ridge in the Waddington Landscape. The Waddington landscape model, proposed in 1957, provides a powerful framework for understanding cell fate determination (Waddington, 1957). As development progresses, cells become restricted to distinct fates, separated by high \"ridges\" that prevent identity switching. A recent study in Nature Genetics uncovers such a ridge in hepatocyte lineage specification (Lim et al., 2025). Lim et al. report that prospero homeobox protein 1 (PROX1) acts as a hepatocyte-specific safeguard repressor, ensuring lineage stability by actively suppressing alternative cell fates and preventing cholangiocarcinoma development.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"102-105"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2025-06-01Epub Date: 2025-05-15DOI: 10.1089/cell.2025.0009
Pedro P Cunha, Mariana Lopes
{"title":"Rejuvenation to the Heart: Overcoming Age-Related Metabolic Barriers in Direct Cardiac Reprogramming.","authors":"Pedro P Cunha, Mariana Lopes","doi":"10.1089/cell.2025.0009","DOIUrl":"10.1089/cell.2025.0009","url":null,"abstract":"<p><p>By dissecting metabolic and epigenetic features imposed by ageing in cardiomyocyte conversion from fetal and adult mouse fibroblasts, Santos et al. describe that metabolic modulation can enhance direct cardiac reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"106-108"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reprogramming Stars #22: Cellular Reprogramming as a Route for Decoding Neurodegenerative Disorders-An Interview with Dr. Janelle Drouin-Ouellet.","authors":"Janelle Drouin-Ouellet, Mariana Lopes, Carlos-Filipe Pereira","doi":"10.1089/cell.2025.77701.int","DOIUrl":"10.1089/cell.2025.77701.int","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"95-101"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2025-06-01Epub Date: 2025-05-15DOI: 10.1089/cell.2025.0008
Giulia Redi, Filomena Del Piano, Sara Cappellini, Martina Paladino, Anne den Breejen, Marcel H A M Fens, Massimiliano Caiazzo
{"title":"Delivery Systems in Neuronal Direct Cell Reprogramming.","authors":"Giulia Redi, Filomena Del Piano, Sara Cappellini, Martina Paladino, Anne den Breejen, Marcel H A M Fens, Massimiliano Caiazzo","doi":"10.1089/cell.2025.0008","DOIUrl":"10.1089/cell.2025.0008","url":null,"abstract":"<p><p>Neuronal direct cell reprogramming approach allows direct conversion of somatic cells into neurons via forced expression of neuronal cell-lineage transcription factors (TFs). These so-called induced neuronal cells have significant potential as research tools and for therapeutic applications, such as in cell replacement therapy. However, the optimization of TF delivery strategies is crucial to reach clinical practice. In this review, we outlined the currently explored delivery technologies in neuronal direct cell reprogramming and their limitations and advantages. The first employed delivery strategies were mainly integrating viral systems, such as lentiviruses that exert consistently high transgene expression in most cell types. On the other hand, viral systems cause major safety concerns, including the risk for insertional mutagenesis and inflammation. More recently, several safer nonviral delivery systems have been investigated as well; however, these systems generally exert inferior reprogramming efficiency compared with viral systems. Emerging delivery technologies could provide new opportunities in the achievement of safe and effective delivery for neuronal direct cell reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"109-123"},"PeriodicalIF":1.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel Insights into the Phospholipase C Delta 3 and Its Implications in Neoplastic Diseases.","authors":"Lindi Xu, Zhenli Li, Shuaishuai Zhu, Xingshun Qi, Wei Zhang, Yufu Tang","doi":"10.1089/cell.2025.0004","DOIUrl":"https://doi.org/10.1089/cell.2025.0004","url":null,"abstract":"<p><p>The phospholipase C (PLC) family plays a crucial role in the construction of biomembranes, cell growth, and signal transduction. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP<sub>3</sub>) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca<sup>2+</sup>) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. Recently, the function of PLC delta 3 (<i>PLCδ3</i>) has been arousing great interests in the basic research of neoplastic diseases. It is demonstrated to affect multiple parts of tumor progression and promote glycolysis reprogramming. However, currently there are no conclusive reports regarding the mechanism of <i>PLCδ3</i>-mediated tumor progression and its importance as a prognostic biomarker in specific neoplastic diseases. Therefore, the present article aimed to illustrate (1) the correlation between the function of phospholipases in PLC family and tumor progression; (2) the <i>PLCδ3</i>-mediated tumor progression, mainly focusing on the signal transduction and regulation; and (3) its potential mechanism and vital targets involved in multiple malignancies.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alice E Lord, Leo J Dudley, Lynette Graver, Gabriella Ficz
{"title":"Old Habits Die Hard: DNA Methylation Patterns Persist in Experimental Transdifferentiation.","authors":"Alice E Lord, Leo J Dudley, Lynette Graver, Gabriella Ficz","doi":"10.1089/cell.2025.0020","DOIUrl":"https://doi.org/10.1089/cell.2025.0020","url":null,"abstract":"<p><p>The reprogramming of somatic cells into different lineages by transdifferentiation holds great promise for regenerative medicine and replacement therapies. However, a recent report by Radwan et al. (PNAS, 2024) finds that transdifferentiated cells fail to fully adopt the DNA methylation profiles of their new lineage. This has important implications regarding the viability of transdifferentiation as a strategy for cell replacement therapy.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2025-04-01Epub Date: 2025-03-20DOI: 10.1089/cell.2024.0066
Kiana Sojoudi, Hossein Azizi, Maryam Solaimani
{"title":"The Proliferation Potential of Differentiated and Undifferentiated Spermatogonial Stem Cells on Diverse Feeder Layers.","authors":"Kiana Sojoudi, Hossein Azizi, Maryam Solaimani","doi":"10.1089/cell.2024.0066","DOIUrl":"10.1089/cell.2024.0066","url":null,"abstract":"<p><p>Spermatogonial stem cells (SSCs) play an essential role in the transfer of genetic information through generations, making studying their cellular and molecular mechanisms critical. However, since SSCs are few in mice, directly studying them is limited, requiring specialized <i>in vitro</i> cultivation. Feeder layers such as mouse embryonic fibroblasts (MEFs), SNL, neonate, and adult mouse testicular stromal feeder cells (TSCs) support <i>in vitro</i> survival and growth. To understand the effectiveness of these feeder layers on SSC proliferation, we compared MEF, SNL, neonatal, and adult TSCs. Furthermore, we identified hub genes and potential pathways in spermatogenesis. Two populations of differentiated and undifferentiated SSCs were compared for mouse SSC colony formation and proliferation effectiveness. Additionally, Cytoscape and STRING databases were employed for protein-protein interaction networks and functional gene enrichment. The expression of three hub genes, including <i>Dazl</i>, <i>Zbtb16</i>, and <i>Stra8</i>, was analyzed using dynamic array chips (Fluidigm) followed by statistical analysis. Our results indicated that undifferentiated SSCs favored MEF feeders, while differentiated SSCs thrived on SNL and primary TSC feeders for long-term culture. Functional enrichment results demonstrated hub genes involvement in cell differentiation, meiosis, regulation of meiotic nuclear division, cell development, and spermatogenesis. Furthermore, mRNA expression levels of <i>Stra8</i>, <i>Zbtb16</i>, and <i>Dazl</i> genes show different patterns among feeder layers and SSC differentiation phases.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":"75-85"},"PeriodicalIF":1.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}