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Stem Cell Metabolism and Diet. 干细胞代谢与饮食
IF 2.3 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-12-01 Epub Date: 2020-10-28 DOI: 10.1007/s40778-020-00180-4
Marine Barthez, Zehan Song, Chih Ling Wang, Danica Chen

Purpose of review: Diet has profound impacts on health and longevity. Evidence is emerging to suggest that diet impinges upon the metabolic pathways in tissue-specific stem cells to influence health and disease. Here, we review the similarities and differences in the metabolism of stem cells from several tissues, and highlight the mitochondrial metabolic checkpoint in stem cell maintenance and aging. We discuss how diet engages the nutrient sensing metabolic pathways and impacts stem cell maintenance. Finally, we explore the therapeutic implications of dietary and metabolic regulation of stem cells.

Recent findings: Stem Cell transition from quiescence to proliferation is associated with a metabolic switch from glycolysis to mitochondrial OXPHOS and the mitochondrial metabolic checkpoint is critically controlled by the nutrient sensors SIRT2, SIRT3, and SIRT7 in hematopoietic stem cells. Intestine stem cell homeostasis during aging and in response to diet is critically dependent on fatty acid metabolism and ketone bodies and is influenced by the niche mediated by the nutrient sensor mTOR.

Summary: Nutrient sensing metabolic pathways critically regulate stem cell maintenance during aging and in response to diet. Elucidating the molecular mechanisms underlying dietary and metabolic regulation of stem cells provides novel insights for stem cell biology and may be targeted therapeutically to reverse stem cell aging and tissue degeneration.

审查目的:饮食对健康和长寿有着深远的影响。越来越多的证据表明,饮食会影响组织特异性干细胞的代谢途径,从而影响健康和疾病。在此,我们回顾了几种组织干细胞代谢的异同,并强调了干细胞维持和衰老过程中的线粒体代谢检查点。我们讨论了饮食如何参与营养传感代谢途径并影响干细胞的维持。最后,我们探讨了干细胞饮食和代谢调节的治疗意义:干细胞从静止到增殖的转变与从糖酵解到线粒体OXPHOS的代谢转换有关,线粒体代谢检查点在造血干细胞中受到营养传感器SIRT2、SIRT3和SIRT7的关键控制。肠干细胞在衰老过程中和饮食反应中的稳态主要依赖于脂肪酸代谢和酮体,并受到营养传感器mTOR介导的生态位的影响。阐明干细胞饮食和代谢调控的分子机制为干细胞生物学提供了新的见解,并可能成为逆转干细胞衰老和组织退化的治疗目标。
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引用次数: 0
Targeting the aryl hydrocarbon receptor in stem cells to improve the use of food as medicine. 靶向干细胞中芳烃受体,提高食品药用价值。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-12-01 Epub Date: 2021-01-05 DOI: 10.1007/s40778-020-00184-0
Huajun Han, Arul Jayaraman, Stephen Safe, Robert S Chapkin

Purpose of review: Intestinal stem cells, the most rapidly proliferating adult stem cells, are exquisitely sensitive to extrinsic dietary factors. Uncontrolled regulation of intestinal stem cells is closely linked to colon tumorigenesis. This review focuses on how dietary and microbial derived cues regulate intestinal stem cell functionality and colon tumorigenesis in mouse models by targeting the aryl hydrocarbon receptor (AhR).

Recent findings: AhR, a ligand activated transcription factor, can integrate environmental, dietary and microbial cues to modulate intestinal stem cell proliferation, differentiation and their microenvironment, affecting colon cancer risk. Modulation of AhR activity is associated with many chronic diseases, including inflammatory bowel diseases where AhR expression is protective.

Summary: AhR signaling controls the maintenance and differentiation of intestinal stem cells, influences local niche factors, and plays a protective role in colon tumorigenesis. Mounting evidence suggests that extrinsic nutritional/dietary cues which modulate AhR signaling may be a promising approach to colon cancer chemoprevention.

综述目的:肠道干细胞是最快速增殖的成体干细胞,对外来饮食因素非常敏感。肠道干细胞不受控制的调控与结肠肿瘤的发生密切相关。本文综述了饮食和微生物来源的线索如何通过靶向芳烃受体(AhR)调节小鼠模型中的肠道干细胞功能和结肠肿瘤发生。最近研究发现:AhR是一种配体激活的转录因子,可以整合环境、饮食和微生物线索,调节肠道干细胞的增殖、分化及其微环境,影响结肠癌风险。AhR活性的调节与许多慢性疾病有关,包括炎症性肠病,其中AhR表达具有保护作用。摘要:AhR信号控制肠道干细胞的维持和分化,影响局部生态位因子,在结肠肿瘤发生过程中发挥保护作用。越来越多的证据表明,调节AhR信号的外部营养/饮食线索可能是一种有希望的结肠癌化学预防方法。
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引用次数: 5
Use of MSCs and MSC-educated macrophages to mitigate hematopoietic acute radiation syndrome. 使用间充质干细胞和培养间充质干细胞的巨噬细胞减轻造血急性放射综合征。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-09-01 Epub Date: 2020-08-08 DOI: 10.1007/s40778-020-00176-0
Raghavan Chinnadurai, Matthew H Forsberg, John A Kink, Peiman Hematti, Christian M Capitini

Purpose of review: Innovative and minimally toxic treatment approaches are sorely needed for the prevention and treatment of hematopoietic acute radiation syndrome (H-ARS). Cell therapies have been increasingly studied for their potential use as countermeasures for accidental and intentional ionizing radiation exposures which can lead to fatal ARS. Mesenchymal stem/stromal cells (MSCs) are a cell therapy that have shown promising results in preclinical studies of ARS, and are being developed in clinical trials specifically for H-ARS. MSCs, MSC-educated macrophages (MEMs) and MSC-exosome educated macrophages (EEMs) all have the potential to be used as adoptive cell therapies for H-ARS. Here we review how MSCs have been reported to mitigate inflammation from radiation injury while also stimulating hematopoiesis during ARS.

Recent findings: We discuss emerging work with immune cell subsets educated by MSCs, including MEMs and EEMs, in promoting hematopoiesis in xenogeneic models of ARS. We also discuss the first placental-derived MSC product to enter phase I trials, PLX-R18, and the challenges faced by bringing MSC and other cell therapies into the clinic for treating ARS.

Summary: Although MSCs, MEMs and EEMs are potential cell therapy candidates in promoting hematopoietic HRS, challenges persist in translational clinical development of these products to the clinic. Whether any of these cellular therapies will be sufficient as stand-alone therapies to mitigate H-ARS or if they will be a bridging therapy that insures survival until a curative allogeneic hematopoietic stem cell transplant can be performed are the key questions that will have to be answered.

综述目的:创新和低毒性的治疗方法是预防和治疗造血急性放射综合征(H-ARS)的迫切需要。细胞疗法已越来越多地研究其潜在的用途,作为对策的意外和故意电离辐射暴露,可导致致命的ARS。间充质干细胞(Mesenchymal stem/stromal cells, MSCs)是一种细胞疗法,在ARS的临床前研究中显示出有希望的结果,并且正在专门针对H-ARS的临床试验中开发。MSCs、msc -转染巨噬细胞(MEMs)和msc -外泌体转染巨噬细胞(EEMs)都有可能被用作H-ARS的过继细胞疗法。在这里,我们回顾了MSCs在ARS期间如何减轻辐射损伤引起的炎症,同时刺激造血的报道。最近的研究结果:我们讨论了由MSCs培养的免疫细胞亚群,包括MEMs和eem,在促进异种ARS模型中的造血方面的新工作。我们还讨论了首个进入I期试验的胎盘源性间充质干细胞产品PLX-R18,以及将间充质干细胞和其他细胞疗法引入临床治疗ARS所面临的挑战。摘要:虽然MSCs、MEMs和EEMs是促进造血HRS的潜在细胞治疗候选细胞,但这些产品在临床转化开发方面仍然存在挑战。这些细胞疗法是否足以作为缓解H-ARS的独立疗法,或者它们是否可以作为桥接疗法,确保存活,直到可以进行治疗性的同种异体造血干细胞移植,这是必须回答的关键问题。
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引用次数: 6
Genome Editing for Rare Diseases. 罕见疾病的基因组编辑。
IF 2.3 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-09-01 Epub Date: 2020-07-07 DOI: 10.1007/s40778-020-00175-1
Arun Pradhan, Tanya V Kalin, Vladimir V Kalinichenko

Purpose of the review: Significant numbers of patients worldwide are affected by various rare diseases, but the effective treatment options to these individuals are limited. Rare diseases remain underfunded compared to more common diseases, leading to significant delays in research progress and ultimately, to finding an effective cure. Here, we review the use of genome-editing tools to understand the pathogenesis of rare diseases and develop additional therapeutic approaches with a high degree of precision.

Recent findings: Several genome-editing approaches, including CRISPR/Cas9, TALEN and ZFN, have been used to generate animal models of rare diseases, understand the disease pathogenesis, correct pathogenic mutations in patient-derived somatic cells and iPSCs, and develop new therapies for rare diseases. The CRISPR/Cas9 system stands out as the most extensively used method for genome editing due to its relative simplicity and superior efficiency compared to TALEN and ZFN. CRISPR/Cas9 is emerging as a feasible gene-editing option to treat rare monogenic and other genetically defined human diseases.

Summary: Less than 5% of ~7000 known rare diseases have FDA-approved therapies, providing a compelling need for additional research and clinical trials to identify efficient treatment options for patients with rare diseases. Development of efficient genome-editing tools capable to correct or replace dysfunctional genes will lead to novel therapeutic approaches in these diseases.

综述的目的:全世界有大量患者受到各种罕见疾病的影响,但这些患者的有效治疗方案却十分有限。与更常见的疾病相比,罕见病的资金仍然不足,导致研究进展严重滞后,最终无法找到有效的治疗方法。在此,我们回顾了如何利用基因组编辑工具来了解罕见病的发病机制,并开发出更多高精度的治疗方法:包括 CRISPR/Cas9、TALEN 和 ZFN 在内的几种基因组编辑方法已被用于生成罕见病的动物模型、了解疾病的发病机制、纠正患者体细胞和 iPSCs 中的致病突变以及开发罕见病的新疗法。CRISPR/Cas9 系统相对简单,与 TALEN 和 ZFN 相比效率更高,因此成为基因组编辑中使用最广泛的方法。CRISPR/Cas9正在成为治疗罕见单基因疾病和其他基因定义的人类疾病的一种可行的基因编辑方法。摘要:在已知的约 7000 种罕见疾病中,只有不到 5%的疾病有美国食品及药物管理局批准的疗法,因此迫切需要开展更多的研究和临床试验,以确定罕见病患者的有效治疗方案。开发能够纠正或替换功能失调基因的高效基因组编辑工具将为这些疾病带来新的治疗方法。
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引用次数: 0
Mechanoregulation in hematopoiesis and hematologic disorders. 造血和血液学疾病的机械调节。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-09-01 Epub Date: 2020-05-21 DOI: 10.1007/s40778-020-00172-4
Paulina D Horton, Sandeep Dumbali, Pamela L Wenzel

Purpose of review: Hematopoietic stem cells (HSCs) are reliant on intrinsic and extrinsic factors for tight control of self-renewal, quiescence, differentiation, and homing. Given the intimate relationship between HSCs and their niche, increasing numbers of studies are examining how biophysical cues in the hematopoietic microenvironment impact HSC functions.

Recent findings: Numerous mechanosensors are present on hematopoietic cells, including integrins, mechanosensitive ion channels, and primary cilia. Integrin-ligand adhesion, in particular, has been found to be critical for homing and anchoring of HSCs and progenitors in the bone marrow. Integrin-mediated interactions with ligands present on extracellular matrix and endothelial cells are key to establishing long-term engraftment and quiescence of HSCs. Importantly, disruption in the architecture and cellular composition of the bone marrow associated with conditioning regimens and primary myelofibrosis exposes HSCs to a profoundly distinct mechanical environment, with potential implications for progression of hematologic dysfunction and pathologies.

Summary: Study of the mechanobiological signals that govern hematopoiesis represents an important future step toward understanding HSC biology in homeostasis, aging, and cancer.

综述目的:造血干细胞(hsc)依赖于内在和外在因素来严格控制自我更新、静止、分化和归巢。鉴于造血干细胞与其生态位之间的密切关系,越来越多的研究正在研究造血微环境中的生物物理线索如何影响造血干细胞的功能。近期发现:造血细胞上存在大量的机械传感器,包括整合素、机械敏感离子通道和初级纤毛。特别是整合素配体的粘附,对于造血干细胞和祖细胞在骨髓中的归巢和锚定至关重要。整合素介导的与细胞外基质和内皮细胞上的配体的相互作用是建立造血干细胞长期植入和静止的关键。重要的是,与调节方案和原发性骨髓纤维化相关的骨髓结构和细胞组成的破坏使造血干细胞暴露在一个非常不同的机械环境中,这可能影响血液功能障碍和病理的进展。摘要:对控制造血的机械生物学信号的研究是理解造血干细胞生物学在体内平衡、衰老和癌症中的重要一步。
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引用次数: 9
Hematopoietic Stem Cells in Health and Disease—Insights from Single-Cell Multi-omic Approaches 造血干细胞在健康和疾病中的作用——来自单细胞多组学方法的见解
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-07-06 DOI: 10.1007/s40778-020-00174-2
S. Haas
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引用次数: 6
In Vivo Genome Engineering for the Treatment of Muscular Dystrophies 体内基因组工程治疗肌肉萎缩症
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-06-19 DOI: 10.1007/s40778-020-00173-3
M. Kustermann, M. Rok, R. Cohn, E. Ivakine
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引用次数: 2
Virus-specific T cells for malignancies - then, now and where to? 针对恶性肿瘤的病毒特异性T细胞——过去、现在和去向?
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-06-01 Epub Date: 2020-05-07 DOI: 10.1007/s40778-020-00170-6
Sandhya Sharma, Wingchi K Leung, Helen E Heslop

Purpose of review: Virus-associated malignancies are a global health burden, constituting 10-12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses.

Recent findings: Initial studies in 1990s first showed that VSTs specific for the Epstein-Barr virus (EBVSTs) can induce complete remissions in patients with post-transplant lymphoproliferative disease. Since then, studies have validated the specificity and safety of VSTs in multiple lymphomas and solid malignancies. However, challenges remain to optimize this platform for widespread use, including enhancing potency and persistence, overcoming the immunosuppressive tumor microenvironment, and streamlining manufacturing processes that comply with regulatory requirements.

Summary: This review focuses on data from clinical trials evaluating VSTs directed against three viruses (EBV, HPV and MCPyV), as well as recent preclinical and clinical advances, and potential future directions.

综述目的:病毒相关恶性肿瘤是全球健康负担,占全球癌症的10-12%。由于这些肿瘤表达可以引起特异性T细胞反应的外来病毒抗原,因此病毒定向免疫疗法是一种很有前途的治疗策略。具体来说,病毒特异性T细胞(VSTs)的过继细胞转移已经证明了根除与某些病毒相关的癌症的潜力。最近的发现:20世纪90年代的初步研究首次表明,EBVSTs可以诱导移植后淋巴细胞增生性疾病患者的完全缓解。从那时起,研究证实了vst在多发性淋巴瘤和实体恶性肿瘤中的特异性和安全性。然而,优化该平台以广泛使用仍然存在挑战,包括增强效力和持久性,克服免疫抑制肿瘤微环境,以及简化符合监管要求的制造过程。摘要:本文综述了针对三种病毒(EBV、HPV和MCPyV)的VSTs的临床试验数据,以及最近的临床前和临床进展,以及潜在的未来方向。
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引用次数: 3
Cell Therapy for Lung Disease: Current Status and Future Prospects 肺部疾病的细胞治疗:现状与展望
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-05-15 DOI: 10.1007/s40778-020-00171-5
S. Rolandsson Enes, D. Weiss
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引用次数: 10
The Role of ASXL1/2 and Their Associated Proteins in Malignant Hematopoiesis ASXL1/2及其相关蛋白在恶性造血中的作用
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-01-21 DOI: 10.1007/s40778-020-00168-0
Peng Zhang, Mingjiang Xu, Feng-Chun Yang
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引用次数: 4
期刊
Current Stem Cell Reports
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