Stem cells and development最新文献

{"title":"Role of Histamine H₃ Receptor Antagonist Pitolisant in Early Neural Differentiation of Mouse Embryonic Stem Cells.","authors":"Genghua Xu, Nuoya Liu, Yaqing Qiu, Jiayu Qi, Danyan Zhu","doi":"10.1089/scd.2023.0162","DOIUrl":"10.1089/scd.2023.0162","url":null,"abstract":"<p><p>The histamine H₃ receptor, prominently expressed in neurons with a minor presence in glial cells, acts as both an autoreceptor and an alloreceptor, controlling the release of histamine and other neurotransmitters. The receptor impacts various essential physiological processes. Our team's initial investigations had demonstrated that the histamine H₃ receptor antagonists could facilitate nerve regeneration by promoting the histamine H₁ receptors on primary neural stem cells (NSCs) in the traumatic brain injury mouse, which suggested the potential of histamine H₃ receptor as a promising target for treating neurological disorders and promoting nerve regeneration. Pitolisant (PITO) is the only histamine H₃ receptor antagonist approved by the Food and Drug Administration (FDA) for treating narcolepsy. However, there is no report on Pitolisant in neural development or regeneration, and it is urgent to be further studied in strong biological activity models in vitro. The embryonic stem (ES) cells were differentiated into neural cells in vitro, which replicated the neurodevelopmental processes that occur in vivo. It also provided an alternative model for studying neurodevelopmental processes and testing drugs for neurological conditions. Therefore, we aimed to elucidate the regulatory role of Pitolisant in the early differentiation of ES cells into neural cells. Our results demonstrated that Pitolisant could promote the differentiation of ES cells toward NSCs and stimulated the formation of growth cones. Furthermore, Pitolisant was capable of inducing the polarization of NSCs through the cAMP-LKB1-SAD/MARK2 pathway, but had no significant effect on later neuronal maturation. Pitolisant altered mitochondrial morphology and upregulated the levels of mitochondrion-related proteins TOM20, Drp1, and p-Drp1, and reversed the inhibitory effect of Mdivi-1 on mitochondrial fission during the early neural differentiation of ES cells. In addition, Pitolisant induced the increase in cytosolic Ca²⁺. Our study provided an experimental foundation for the potential application of histamine H₃ receptor-targeted modulators in the field of neuroregeneration.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.","authors":"Didem Yilmaz-Oral, Sena F Sezen, Damla Turkcan, Heba Asker, Ecem Kaya-Sezginer, Omer Faruk Kirlangic, Cagla Zubeyde Kopru, Mualla Pınar Elci, Fatma Zeynep Ozen, Petek Korkusuz, Sema Oren, Cetin Volkan Oztekin, Ilker Ates, Serap Gur","doi":"10.1089/scd.2023.0178","DOIUrl":"10.1089/scd.2023.0178","url":null,"abstract":"<p><p>As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (<i>n</i> = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 10⁶ cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Temporal Wnt Signal for Efficient Differentiation of Intestinal Stem Cells in an Organoid Model.","authors":"Li Yang, Xulei Wang, Guoqing Zhao, Liling Deng, Xiaolei Yin","doi":"10.1089/scd.2023.0186","DOIUrl":"10.1089/scd.2023.0186","url":null,"abstract":"<p><p>The homeostasis of the intestinal epithelium heavily relies on the self-renewal and differentiation of intestinal stem cells (ISCs). Although the orchestration of these processes by signaling pathways such as the Wnt, BMP, Notch, and MAPK signals has been extensively studied, the dynamics of their regulation remains unclear. Our study explores how the Wnt signaling pathway temporally regulates the differentiation of ISCs into various cell types in an intestinal organoid system. We report that the duration of Wnt exposure following Notch pathway inactivation significantly influences the differentiation direction of intestinal epithelial cells toward multiple secretory cell types, including goblet cells, enteroendocrine cells (EECs), and Paneth cells. This temporal regulation of Wnt signaling adds another layer of complexity to the combination of niche signals that govern cell fate. By manipulating this temporal signal, we have developed optimized protocols for the efficient in vitro differentiation of ISCs into EECs and goblet cells. These findings provide critical insights into the dynamic regulation of ISC differentiation and offer a robust platform for future investigations into intestinal biology and potential therapeutic applications.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61567108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Mesenchymal Stem Cells in Hair Regeneration and Hair Cycle.","authors":"Cong Ma, Ming Cheng, Yan Wu, Xuegang Xu","doi":"10.1089/scd.2023.0156","DOIUrl":"10.1089/scd.2023.0156","url":null,"abstract":"<p><p>The health of hair is directly related to people's health and appearance. Hair has key physiological functions, including skin protection and temperature regulation. Hair follicle (HF) is a vital mini-organ that directly impacts hair growth. Besides, various signaling pathways and molecules regulate the growth cycle transition of HFs. Hair and its regeneration studies have attracted much interest in recent years with the increasing rate of alopecia. Mesenchymal stem cells (MSCs), as pluripotent stem cells, can differentiate into fat, bone, and cartilage and stimulate regeneration and immunological regulation. MSCs have been widely employed to treat various clinical diseases, such as bone and cartilage injury, nerve injury, and lung injury. Besides, MSCs can be used for treatment of hair diseases due to their regenerative and immunomodulatory abilities. This review aimed to assess MSCs' treatment for alopecia, pertinent signaling pathways, and new material for hair regeneration in the last 5 years.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/scd.2023.29016.ack","DOIUrl":"https://doi.org/10.1089/scd.2023.29016.ack","url":null,"abstract":"","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Cell Replacement of Human Veins, Modeling Vascular Repair and Endothelial Cell Chimerism.","authors":"Hector Tejeda-Mora, Yvette den Hartog, Ivo J Schurink, Monique M A Verstegen, Jeroen de Jonge, Martijn W F van den Hoogen, Carla C Baan, Robert C Minnee, Martin J Hoogduijn, Luc J W van der Laan, Jorke Willemse","doi":"10.1089/scd.2023.0142","DOIUrl":"10.1089/scd.2023.0142","url":null,"abstract":"<p><p>Allogeneic transplant organs are potentially highly immunogenic. The endothelial cells (ECs) located within the vascular system serve as the primary interface between the recipient's immune system and the donor organ, playing a key role in the alloimmune response. In this study, we investigated the potential use of recipient-derived ECs in a vein recellularization model. In this study, human iliac veins underwent complete decellularization using a Triton X-100 protocol. We demonstrated the feasibility of re-endothelializing acellular blood vessels using either human umbilical cord vein endothelial cell or human venous-derived ECs, with this re- endothelialization being sustainable for up to 28 days in vitro. The re-endothelialized veins exhibited the restoration of vascular barrier function, along with the restoration of innate immunoregulatory capabilities, evident through the facilitation of monocytic cell transmigration and their polarization toward a macrophage phenotype following transendothelial extravasation. Finally, we explored whether recellularization with EC of a different donor could prevent antibody-mediated rejection. We demonstrated that in chimeric vessels, allogeneic EC became a target of the humoral anti-donor response after activation of the classical immune complement pathway whereas autologous EC were spared, emphasizing their potential utility before transplantation. In conclusion, our study demonstrates that replacement of EC in transplants could reduce the immunological challenges associated with allogeneic grafts.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/scd.2023.29016.ack","DOIUrl":"https://doi.org/10.1089/scd.2023.29016.ack","url":null,"abstract":"","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do We Establish a Cold Chain Preservation Process Leading to Warmed Healthy Cells?","authors":"Steve Oh","doi":"10.1089/scd.2023.0225","DOIUrl":"10.1089/scd.2023.0225","url":null,"abstract":"NA.","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41242759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA-Seq Analysis Identifies Angiotensinogen and Galanin as Unique Molecular Markers of Acinar Cells in Murine Salivary Glands.","authors":"Jingming Liu, Yanan Li, Yuxin Zhang, Qianyu Cheng, Huikai Liu, Liwen He, Liang Chen, Tianyu Zhao, Panpan Liang, Wenping Luo","doi":"10.1089/scd.2023.0125","DOIUrl":"10.1089/scd.2023.0125","url":null,"abstract":"<p><p>The submandibular gland (SMG) and sublingual gland (SLG) are two of three major salivary glands in mammals and comprise serous and mucous acinar cells. The two glands share some functional properties, which are largely dependent on the types of acinar cells. In recent years, while ScRNA-seq (single-cell sequencing) with a 10 × platform has been used to explore molecular markers in salivary glands, few studies have examined the acinar heterogeneity and unique molecular markers between SMG and SLG. This study aimed to identify the molecular markers of acinar cells in the SLG and SMG. We performed ScRNA-seq analyses in 4-week-old mice and verified the screened molecular markers using reverse transcription-quantitative real-time PCR, immunohistochemistry, and immunofluorescence. Our results showed prominently heterogeneous acinar cells, although there was great similarity in the cluster composition between the two glands at 4 weeks. Furthermore, we demonstrated that <i>Agt</i> is a specific marker of SMG serous acinar cells, whereas <i>Gal</i> is a specific marker of SLG mucous acinar cells. Trajectory inference revealed that <i>Agt</i> and <i>Gal</i> represent two types of differential acinar cell clusters during late development in adults. Thus, we reveal previously unknown specific markers for salivary acinar cell diversity, which has extensive implications for their further functional research.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Reproducible and Scalable Culture Conditions for In Vitro Maintenance of Pig Embryonic Stem Cells Using the Sandoz Inbred Swiss Mouse Thioguanine-Resistant Ouabain-Resistant Cell Line as a Feeder Layer.","authors":"Yelim Ahn, Jinsol Jeong, Kwang-Hwan Choi, Dong-Kyung Lee, Mingyun Lee, Na-Young Lee, Dae-Yong Kim, Chang-Kyu Lee","doi":"10.1089/scd.2023.0171","DOIUrl":"10.1089/scd.2023.0171","url":null,"abstract":"<p><p>Feeder cells play a crucial role in maintaining the pluripotency of embryonic stem cells (ESCs) by secreting various extrinsic regulators, such as extracellular matrix (ECM) proteins and growth factors. Although primary mouse embryonic fibroblasts (MEFs) are the most widely used feeder cell type for the culture of ESCs, they have inevitable disadvantages such as batch-to-batch variation and labor-intensive isolation processes. Here, we revealed that the Sandoz inbred Swiss Mouse (SIM) thioguanine-resistant ouabain-resistant (STO) cell line, an immortalized cell line established from mouse SIM embryonic fibroblasts, can be used as a feeder layer for in vitro culture of authentic pig ESCs instead of primary MEFs. First, the expression of genes encoding ECM proteins and growth factors was analyzed to compare their secretory functions as feeder cells. Quantitative real-time polymerase chain reaction (qPCR) showed that the gene expression of these pluripotency-associated factors was downregulated in STO cells compared to primary MEFs of similar density. Therefore, subsequent optimization of the culture conditions was attempted using higher STO cell densities. Notably, pig ESCs cultured on STO cell density of 3 × (187,500 cells/cm²) exhibited the most similar pluripotent state to pig ESCs cultured on primary MEF density of 1 × (62,500 cells/cm²), as determined by alkaline phosphatase staining, qPCR, and immunocytochemistry. In addition, pig ESCs cultured on STO cell density of 3 × formed complex teratoma containing multiple types of tissues derived from all three germ layers. Our culture conditions using optimal STO cell density can be applied to fields requiring reproducible and scalable production of pig ESCs, such as preclinical research and cellular agriculture.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}