Handi Cao, Sanxing Gao, Ritika Jogani, Ryohichi Sugimura
{"title":"The Tumor Microenvironment Reprograms Immune Cells.","authors":"Handi Cao, Sanxing Gao, Ritika Jogani, Ryohichi Sugimura","doi":"10.1089/cell.2022.0047","DOIUrl":"https://doi.org/10.1089/cell.2022.0047","url":null,"abstract":"<p><p>Tumor tissue comprises a highly complex network of diverse cell types. The tumor microenvironment (TME) can be mainly subdivided into cancer cells and stromal cell compartments, the latter include different types of immune cells, fibroblasts, endothelial cells, and pericytes. Tumor cells reprogram immune cells and other stromal cells in the TME to constrain their antitumor capacity by creating an immunosuppressive milieu and metabolism competition. Moreover, the reprogramming effect on immune cells is localized not only in the tumor but also at the systemic level. With wide application of single-cell sequencing technology, tumor-specific characteristics of immune cells and other stromal cells in the TME have been dissected. In this review, we mainly focus on how tumor cells reprogram immune cells both within the TME and peripheral blood. This information can further help us to improve the efficiency of current immunotherapy as well as bring up new ideas to combat cancer.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"24 6","pages":"343-352"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10572719","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":"The Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus.","authors":"Liang Zhu, Sheng Wang, JunSheng Qu, Zongguang Hui, Chengxia Kan, Ningning Hou, Xiaodong Sun","doi":"10.1089/cell.2022.0039","DOIUrl":"https://doi.org/10.1089/cell.2022.0039","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) exist in many tissues and can differentiate into cells of multiple lineages, such as adipocytes, osteoblasts, or chondrocytes. MSC administration has demonstrated therapeutic potential in various degenerative and inflammatory diseases (<i>e.g.</i>, graft-vs.-host disease, multiple sclerosis, Crohn's disease, organ fibrosis, and diabetes mellitus [DM]). The mechanisms involved in the therapeutic effects of MSCs are multifaceted. Generally, implanted MSCs can migrate to sites of injury, where they establish an anti-inflammatory and regenerative microenvironment in damaged tissues. In addition, MSCs can modulate innate and adaptive immune responses through immunosuppressive mechanisms that involve immune cells, inflammatory cytokines, chemokines, and immunomodulatory factors. DM has a high prevalence worldwide; it also contributes to a high rate of mortality worldwide. MSCs offer a promising therapeutic agent to prevent or repair damage from DM and diabetic complications through properties such as multilineage differentiation, homing, promotion of angiogenesis, and immunomodulation (<i>e.g.</i>, prevention of oxidative stress, fibrosis, and cell death). In this study, we review current findings regarding the immunomodulatory and regenerative mechanisms of MSCs, as well as their therapeutic applications in DM and DM-related complications.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"24 6","pages":"329-342"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10574455","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}
Lena Böhnke, Lucia Zhou-Yang, Silvia Pelucchi, Flora Kogler, Daniela Frantal, Florian Schön, Stina Lagerström, Oliver Borgogno, Jennifer Baltazar, Joseph R Herdy, Sarah Kittel-Schneider, Michaela Defrancesco, Jerome Mertens
{"title":"Chemical Replacement of Noggin with Dorsomorphin Homolog 1 for Cost-Effective Direct Neuronal Conversion.","authors":"Lena Böhnke, Lucia Zhou-Yang, Silvia Pelucchi, Flora Kogler, Daniela Frantal, Florian Schön, Stina Lagerström, Oliver Borgogno, Jennifer Baltazar, Joseph R Herdy, Sarah Kittel-Schneider, Michaela Defrancesco, Jerome Mertens","doi":"10.1089/cell.2021.0200","DOIUrl":"https://doi.org/10.1089/cell.2021.0200","url":null,"abstract":"<p><p>The direct conversion of adult human skin fibroblasts (FBs) into induced neurons (iNs) represents a useful technology to generate donor-specific adult-like human neurons. Disease modeling studies rely on the consistently efficient conversion of relatively large cohorts of FBs. Despite the identification of several small molecular enhancers, high-yield protocols still demand addition of recombinant Noggin. To identify a replacement to circumvent the technical and economic challenges associated with Noggin, we assessed dynamic gene expression trajectories of transforming growth factor-β signaling during FB-to-iN conversion. We identified ALK2 (ACVR1) of the bone morphogenic protein branch to possess the highest initial transcript abundance in FBs and the steepest decline during successful neuronal conversion. We thus assessed the efficacy of dorsomorphin homolog 1 (DMH1), a highly selective ALK2-inhibitor, for its potential to replace Noggin. Conversion media containing DMH1 (+DMH1) indeed enhanced conversion efficiencies over basic SMAD inhibition (tSMADi), yielding similar βIII-tubulin (TUBB3) purities as conversion media containing Noggin (+Noggin). Furthermore, +DMH1 induced high yields of iNs with clear neuronal morphologies that are positive for the mature neuronal marker NeuN. Validation of +DMH1 for iN conversion of FBs from 15 adult human donors further demonstrates that Noggin-free conversion consistently yields iN cultures that display high βIII-tubulin numbers with synaptic structures and basic spontaneous neuronal activity at a third of the cost.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"24 5","pages":"304-313"},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cellular reprogrammingPub Date : 2022-10-01Epub Date: 2022-07-15DOI: 10.1089/cell.2022.0048
Jonathan L Colarusso, Qiao Zhou
{"title":"Direct Reprogramming of Different Cell Lineages into Pancreatic β-Like Cells.","authors":"Jonathan L Colarusso, Qiao Zhou","doi":"10.1089/cell.2022.0048","DOIUrl":"10.1089/cell.2022.0048","url":null,"abstract":"<p><p>One major goal of regenerative medicine is the production of pancreatic endocrine islets to treat insulin-dependent diabetic patients. Among the different methods developed to achieve this goal, a particularly promising approach is direct lineage reprogramming, in which non-β-cells are directly converted to glucose-responsive, insulin-secreting β-like cells. Efforts by different research groups have led to critical insights in the inducing factors necessary and types of somatic tissues suitable for direct conversion to β-like cells. Nevertheless, there is limited understanding of the molecular mechanisms underlying direct cell fate conversion. Significant challenges also remain in translating discoveries into therapeutics that will eventually benefit diabetic patients. This review aims to cover the advances made in the direct reprogramming of somatic cells into β-like cells and discuss the remaining challenges.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"24 5","pages":"252-258"},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634980/pdf/cell.2022.0048.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10470590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongxia Xu, Xuguang Wang, Ruixin Tao, Jiaying Bi, Xu He, Fuquan Zhu, Ke-wei Liu, Yinxue Xu, Juan Li
{"title":"Optimal Stage for Cryotop Vitrification of Porcine Embryos.","authors":"Hongxia Xu, Xuguang Wang, Ruixin Tao, Jiaying Bi, Xu He, Fuquan Zhu, Ke-wei Liu, Yinxue Xu, Juan Li","doi":"10.1089/cell.2022.0001","DOIUrl":"https://doi.org/10.1089/cell.2022.0001","url":null,"abstract":"Different development stages of porcine embryos have different tolerance to low temperature. Therefore, we took the porcine embryos after parthenogenetic activation (PA) as the model, to explore the optimal development stage for vitrification during morula (D4), early blastocyst (D5), and expanded blastocyst (D6) after PA (D0). Embryos were observed with microscope and analyzed by different staining after cryo-recovery for 24 hours. The quality of embryos was damaged after vitrification, including embryonic nuclei, DNA, cytoskeleton, and organelles. The re-expansion rate at 24 hours of D5 embryos was significantly higher than those of D4 and D6 embryos (D5 vs. D4 vs. D6, 27.620 ± 0.041 vs. 7.809 ± 0.027 vs. 13.970 ± 0.032, p < 0.05). Therefore, D5 embryos were selected as research objects to explore the effect of vitrification on lipid in vitrified embryos. The results showed that the expression levels of perilipin PLIN3 messenger RNA (mRNA) and triacylglycerol synthesis-related genes AGPAT1 and DGAT mRNA are significantly reduced (p < 0.05). Vitrification affected lipid synthesis, which might have an irreversible impact on embryonic development. In conclusion, our data demonstrated that the optimal stage of vitrification was D5 for early blastocysts.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"24 3 1","pages":"132-141"},"PeriodicalIF":1.6,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43794724","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":"Preconditioning with Trehalose Protects the Bone Marrow-Derived Mesenchymal Stem Cells Under Oxidative Stress and Enhances the Stem Cell-Based Therapy for Cerebral Ischemic Stroke.","authors":"Bing Shu, Jingsong Wan, Xiang Li, Raynald Liu, Cheng-shi Xu, Yihua An, Jingcao Chen","doi":"10.1089/cell.2022.0037","DOIUrl":"https://doi.org/10.1089/cell.2022.0037","url":null,"abstract":"Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3, Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of hydrogen peroxide (H2O2). Enzyme-linked immunosorbent assay was used to test the secretion levels of neurotrophic factors. An in vivo ischemia/reperfusion model was generated by middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of ischemia/reperfusion injury.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41848320","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":"In Vitro Induction of Human Dental Pulp Stem Cells to Lymphatic Endothelial Cells.","authors":"Shuqun Qi, L. Ye, Liru Hu, Jian Pan","doi":"10.1089/cell.2021.0106","DOIUrl":"https://doi.org/10.1089/cell.2021.0106","url":null,"abstract":"Lymphedema is a progressive and irreversible disease due to the lymphatic system disorder. Conservative and surgical therapies are either ineffective or impractical. Currently, mesenchymal stem cells (MSCs)-based therapies seem to be the most promising treatment for lymphedema. The MSCs promote lymphangiogenesis through the paracrine approach or by directly differentiating into lymphatic endothelial cells (LECs) under the induction of growth factors. Human dental pulp stem cells (hDPSCs) have been suggested to play important roles in tissue regeneration, making it an attractive candidate for the lymphedema treatment. In this study, to evaluate the potential role of hDPSCs in the clinical application for lymphedema treatment, we induced the hDPSCs with vascular endothelial growth factor-C (VEGF-C) and investigated the lymphangiogenic differentiation potential of hDPSCs in vitro. We found that under the VEGF-C induction, hDPSCs demonstrated upregulated LECs specific markers, promoted cell proliferation and migration, and increased tube formation, all of which contributed to their differentiation into LECs in vitro.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45529789","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":"An Alternative Way to Improve Mammalian Embryo Development In Vitro: Culture of Zona Pellucida-Free Embryos.","authors":"Sarah Madani, Z. Machaty, G. Vajta","doi":"10.1089/cell.2022.0012","DOIUrl":"https://doi.org/10.1089/cell.2022.0012","url":null,"abstract":"An increasing number of data proves that the presence of the zona pellucida is not essential to mammalian embryo production, including maturation, fertilization, and embryo culture. In fact, the structure of the zona pellucida of in vitro-produced embryos differs significantly from its in vivo counterpart, influencing metabolism and requiring disproportionate efforts to crack open at the time of hatching. This review aims to focus attention on this field and stimulate research in zona-free embryo culture. In domestic animals, extensive application of purpose-designed culture systems for zona-free embryos proved the feasibility of this approach. It may open new possibilities and increase efficiency in both transgenic research and human-assisted reproduction.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42588196","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":"Effects of Trichostatin A on the Timing of the First Cleavage and In Vitro Developmental Potential of Bovine Somatic Cell Nuclear Transfer Embryos.","authors":"S. Akagi, K. Matsukawa","doi":"10.1089/cell.2022.0003","DOIUrl":"https://doi.org/10.1089/cell.2022.0003","url":null,"abstract":"This study examined the relationship between the timing of the first cleavage and in vitro development of bovine somatic cell nuclear transfer (SCNT) embryos treated with trichostatin A (TSA). SCNT embryos were visually assessed at 22, 26, and 48 hours after activation. Each embryo with two or more distinct blastomeres was transferred into a microwell and cultured until day 7. Irrespective of TSA treatment, approximately half of the cleaved embryos were observed at 22 hours, and a significantly higher blastocyst formation rate was shown in the SCNT embryos cleaved at 22 hours than those cleaved at ≥26 hours. The blastocyst formation rate of TSA-treated embryos cleaved at 22 hours (80%) was slightly higher than that of the control embryos (70%). In addition, interferon-τ (IFN-τ) expression was significantly lower in control SCNT embryos and late-cleaving (>26 hours) TSA-treated embryos than in in vitro fertilized (IVF) embryos. However, a significant difference was not observed between TSA-treated SCNT embryos cleaved at 22 and 26 hours, and IVF embryos. These results suggest that TSA treatment has no influence on the timing of the first cleavage of SCNT embryos; however, it slightly improves the blastocyst formation rate and the expression level of IFN-τ in early-cleaving embryos.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":"1 1","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41346897","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}