{"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":null,"pages":null},"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}
{"title":"Synthetic Embryos Can Complete Gastrulation and Initiate Organogenesis <i>Ex Utero</i>.","authors":"Alejo E Rodriguez-Fraticelli","doi":"10.1089/cell.2022.0111","DOIUrl":"https://doi.org/10.1089/cell.2022.0111","url":null,"abstract":"<p><p>Developmental biology has been revolutionized by two recent articles showing that synthetic mouse embryos derived from embryonic stem cells (ESCs) can be grown <i>ex vivo</i> and complete gastrulation up to the organogenesis stage. This is a remarkable achievement that had never been attained using stem cells before. Both studies used transcription factors to reprogram extraembryonic cells, which they combined with naive ESCs. Further culture of these aggregates using gas-exchange bioreactors allowed these aggregates to proceed through gastrulation and organogenesis, resembling E8.5 stage mouse embryos. These advanced synthetic embryos will allow the modeling of challenging stages of mammalian development. Translation of these findings to human pluripotent systems may allow the production of rare cell types for engineering and therapy.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33499154","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}
Janelle Drouin-Ouellet, Dan Li, Yuancheng Ryan Lu, Camila Vazquez Echegaray
{"title":"The 2022 International Society for Stem Cell Research (ISSCR) Annual Meeting: Celebrating 20 Years of Achievements.","authors":"Janelle Drouin-Ouellet, Dan Li, Yuancheng Ryan Lu, Camila Vazquez Echegaray","doi":"10.1089/cell.2022.0105","DOIUrl":"https://doi.org/10.1089/cell.2022.0105","url":null,"abstract":"<p><p>Last June, the stem cell community came together to celebrate the 20th anniversary of the International Society for Stem Cell Research (ISSCR), one of the leading organizations in the field. The hybrid event mixed a varied program filled with plenary talks, concurrent track sessions, poster presentations, exhibit booths, and plenty of opportunities to enhance stem cell research through bonding between academia and industry. This report highlights the Plenary sessions, with the main topics discussed by each speaker. All the impressive research showcased during the meeting is genuine proof of the great advancements the field has witnessed during these last 20 years, and the more to come.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33499155","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":"Past, Present, and Future of Direct Cell Reprogramming.","authors":"Henrik Ahlenius","doi":"10.1089/cell.2022.0110","DOIUrl":"https://doi.org/10.1089/cell.2022.0110","url":null,"abstract":"<p><p>Budding off from the broader developmental biology and stem cell research fields, cellular reprogramming is now established as a prominent discipline in its own right. Direct cell reprogramming is defined as the cell fate conversion of a somatic cell toward another identity without a pluripotent intermediate state. In addition to the opportunity for mechanistic dissection of lineage commitment in human cells, the field offer the promise of diverse applications such as for disease modeling, cell replacement therapy, regenerative medicine, and immunotherapy that have recently spurred innovation and out of the box thinking to unleash the potential of cellular plasticity.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33498680","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":"Appropriate Exogenous Expression Stoichiometry of GATA4 as an Important Factor for Cardiac Reprogramming of Human Dermal Fibroblasts.","authors":"Xiangyu Zhang, Qi Zhang, Lijun Chen, Baomei Cai, Mengying Zeng, Sihua Ou, Yating Chen, Ziyu Feng, Huan Chen, Shangtao Cao, Kai Kang","doi":"10.1089/cell.2022.0014","DOIUrl":"https://doi.org/10.1089/cell.2022.0014","url":null,"abstract":"<p><p>Reprogramming of human dermal fibroblasts (HDFs) into induced cardiomyocyte-like cells (iCMs) represents a promising strategy for human cardiac regeneration. Different cocktails of cardiac transcription factors can convert HDFs into iCMs, although with low efficiency and immature phenotype. Here, GATA4, MEF2C, TBX5, MESP1, and MYOCD (GMTMeMy for short) were used to reprogram HDFs by retrovirus infection. We found that the exogenous expression stoichiometry of GATA4 (GATA4 stoichiometry) significantly affected reprogramming efficiency. When 1/8 dosage of GATA4 virus (GATA4 dosage) plus MTMeMy was used, the reprogramming efficiency was obviously improved compared with average pooled virus encoding each factor, which measured, by the expression level of cardiac genes, the percentage of cardiac troponin T and alpha-cardiac myosin heavy-chain immunopositive cells and the numbers of iCMs showing calcium oscillation or beating synchronously in co-culture with mouse CMs. In addition, we prepared conditioned maintenance medium (CMM) by CM differentiation of H9 human embryonic stem cell line. We found that compared with traditional maintenance medium (TMM), CMM made iCMs show well-organized sarcomere formation and characteristic calcium oscillation wave earlier. These findings demonstrated that appropriate GATA4 stoichiometry was essential for cardiac reprogramming and some components in CMM were important for maturation of iCMs.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405502","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 : 2022-10-01Epub Date: 2022-07-08DOI: 10.1089/cell.2022.0055
Suleva Povea-Cabello, Marina Villanueva-Paz, Irene Villalón-García, Marta Talaverón-Rey, Mónica Álvarez-Cordoba, Juan M Suárez-Rivero, María Ángeles Montes, Antonio Rodríguez-Moreno, Yuniesky Andrade-Talavera, José A Armengol, José A Sánchez-Alcázar
{"title":"Modeling Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome Using Patient-Derived Induced Neurons Generated by Direct Reprogramming.","authors":"Suleva Povea-Cabello, Marina Villanueva-Paz, Irene Villalón-García, Marta Talaverón-Rey, Mónica Álvarez-Cordoba, Juan M Suárez-Rivero, María Ángeles Montes, Antonio Rodríguez-Moreno, Yuniesky Andrade-Talavera, José A Armengol, José A Sánchez-Alcázar","doi":"10.1089/cell.2022.0055","DOIUrl":"https://doi.org/10.1089/cell.2022.0055","url":null,"abstract":"<p><p>Mitochondrial diseases are a heterogeneous group of rare genetic disorders caused by mutations in nuclear or mitochondrial DNA (mtDNA). These diseases are frequently multisystemic, although mainly affect tissues that require large amounts of energy such as the brain. Mutations in mitochondrial transfer RNA (mt-tRNA) lead to defects in protein translation that may compromise some or all mtDNA-encoded proteins. Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS) syndrome is mainly caused by the m.3243A>G mutation in the mt-tRNA<sup>Leu(UUR)</sup> (<i>MT-TL1</i>) gene. Owing to the lack of proper animal models, several cellular models have been developed to study the disease, providing insight in the pathophysiological mechanisms of MELAS. In this study, we show a successful direct conversion of MELAS patient-derived fibroblasts into induced neurons (iNs) for the first time, as well as an electrophysiological characterization of iNs cocultured with astrocytes. In addition, we performed bioenergetics analysis to study the consequences of m.3243A>G mutation in this neuronal model of MELAS syndrome.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40573081","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":null,"pages":null},"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}
{"title":"Direct Cell Conversion of Somatic Cells into Dopamine Neurons: Achievements and Perspectives.","authors":"Simona Aversano, Renata Palladino, Massimiliano Caiazzo","doi":"10.1089/cell.2022.0065","DOIUrl":"https://doi.org/10.1089/cell.2022.0065","url":null,"abstract":"<p><p>In the last decade, direct reprogramming has emerged as a novel strategy to obtain mature and functional dopamine neurons from somatic cells. This approach could overcome issues linked to the use of human pluripotent stem cells such as ethical concerns and safety problems that can arise from the overgrowth of undifferentiated cells after transplantation. Several conversion methodologies have been developed to obtain induced DA neurons (iDANs) or induced DA neuron progenitors (iDPs). iDANs have also proved to successfully integrate in mice striatum, alleviating Parkinson's disease (PD) motor symptoms. In the next decade, human iDANs and/or iDPs could be translated to clinic to achieve a patient-tailored therapy, but current critical issues hinder this goal, such as the low conversion rate of adult human fibroblasts and the risks associated with lentiviral delivery of conversion factors. In this study, we summarize the strategies and recent improvements developed for the generation of mouse and human iDANs/iDPs. Furthermore, we discuss the more recent application of <i>in vivo</i> direct conversion, which may enable clinical therapies for PD by means of brain <i>in situ</i> delivery of dopaminergic reprogramming transcription factors.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33470864","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":"Small Molecules Pushing Erythroid/Megakaryocyte Cell Specification Boundaries.","authors":"Johan Flygare","doi":"10.1089/cell.2022.0107","DOIUrl":"https://doi.org/10.1089/cell.2022.0107","url":null,"abstract":"<p><p>A combination of a MEK/ERK-signaling inhibitor and three chromatin-remodeling molecules enhances generation of platelet-producing megakaryocytes <i>in vitro</i>, possibly through direct reprogramming.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33499156","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 : 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":null,"pages":null},"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}