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Metabolic Regulation of Stem Cells in Aging. 干细胞衰老过程中的代谢调控
IF 2.3 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-06-01 Epub Date: 2021-04-23 DOI: 10.1007/s40778-021-00186-6
Andrea Keller, Tyus Temple, Behnam Sayanjali, Maria M Mihaylova

Purpose of review: From invertebrates to vertebrates, the ability to sense nutrient availability is critical for survival. Complex organisms have evolved numerous signaling pathways to sense nutrients and dietary fluctuations, which influence many cellular processes. Although both overabundance and extreme depletion of nutrients can lead to deleterious effects, dietary restriction without malnutrition can increase lifespan and promote overall health in many model organisms. In this review, we focus on age-dependent changes in stem cell metabolism and dietary interventions used to modulate stem cell function in aging.

Recent findings: Over the last half-century, seminal studies have illustrated that dietary restriction confers beneficial effects on longevity in many model organisms. Many researchers have now turned to dissecting the molecular mechanisms by which these diets affect aging at the cellular level. One subpopulation of cells of particular interest are adult stem cells, the most regenerative cells of the body. It is generally accepted that the regenerative capacity of stem cells declines with age, and while the metabolic requirements of each vary across tissues, the ability of dietary interventions to influence stem cell function is striking.

Summary: In this review, we will focus primarily on how metabolism plays a role in adult stem cell homeostasis with respect to aging, with particular emphasis on intestinal stem cells while also touching on hematopoietic, skeletal muscle, and neural stem cells. We will also discuss key metabolic signaling pathways influenced by both dietary restriction and the aging process, and will examine their role in improving tissue homeostasis and lifespan. Understanding the mechanisms behind the metabolic needs of stem cells will help bridge the divide between a basic science interpretation of stem cell function and a whole-organism view of nutrition, thereby providing insight into potential dietary or therapeutic interventions.

综述的目的:从无脊椎动物到脊椎动物,感知营养供应的能力对于生存至关重要。复杂的生物体进化出许多信号通路来感知营养物质和膳食波动,从而影响许多细胞过程。虽然营养物质的过度丰富和极度匮乏都会导致有害影响,但在许多模式生物中,在没有营养不良的情况下限制饮食可以延长寿命并促进整体健康。在这篇综述中,我们将重点讨论干细胞新陈代谢随年龄而发生的变化,以及在衰老过程中用于调节干细胞功能的饮食干预措施:在过去的半个世纪中,开创性的研究表明,饮食限制对许多模式生物的长寿具有有益的影响。现在,许多研究人员转而研究这些饮食在细胞水平上影响衰老的分子机制。其中一个特别令人感兴趣的细胞亚群是成体干细胞,它们是人体中最具再生能力的细胞。人们普遍认为,干细胞的再生能力会随着年龄的增长而下降,虽然不同组织对新陈代谢的要求各不相同,但饮食干预对干细胞功能的影响能力是惊人的。摘要:在这篇综述中,我们将主要关注新陈代谢如何在成人干细胞稳态中发挥与衰老有关的作用,特别强调肠道干细胞,同时也涉及造血干细胞、骨骼肌干细胞和神经干细胞。我们还将讨论受饮食限制和衰老过程影响的关键代谢信号通路,并研究它们在改善组织稳态和延长寿命方面的作用。了解干细胞新陈代谢需求背后的机制将有助于弥合干细胞功能基础科学解释与整个有机体营养观点之间的鸿沟,从而为潜在的饮食或治疗干预提供洞察力。
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引用次数: 0
Encapsulation Strategies for Pancreatic Islet Transplantation without Immune Suppression 无免疫抑制的胰岛移植包封策略
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-05-14 DOI: 10.1007/s40778-021-00190-w
S. Sittadjody, E. Opara
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引用次数: 1
Amnion Epithelial Cells — a Therapeutic Source 羊膜上皮细胞-一种治疗来源
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-03-01 DOI: 10.1007/s40778-021-00187-5
R. Schwab, Mihiri Goonetilleke, Dandan Zhu, G. Kusuma, E. Wallace, W. Sievert, R. Lim
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引用次数: 0
Mitochondria Transfer in Bone Marrow Hematopoietic Activity. 骨髓造血活性中的线粒体转移。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-03-01 DOI: 10.1007/s40778-020-00185-z
Abhishek K Singh, Jose A Cancelas

Purpose of review: The well-established crosstalk between hematopoietic stem cells (HSC) and bone marrow (BM) microenvironment is critical for the homeostasis and hematopoietic regeneration in response to blood formation emergencies. Past decade has witnessed that the intercellular communication mediated by the transfer of cytoplasmic material and organelles between cells can regenerate and/or repair the damaged cells. Mitochondria have recently emerged as a potential regulator of HSC fate. This review intends to discuss recent advances in the understanding of the mitochondrial dynamics, specifically focused on the role of mitochondrial transfer, in the maintenance of HSC activity with clear implications in stem cell transplantation and regenerative medicine.

Recent findings: HSC are highly heterogeneous in their mitochondrial metabolism, and the quiescence and potency of HSC depend on the status of mitochondrial dynamics and the clearance of damaged mitochondria. Recent evidence has shown that in stress response, BM stromal cells transfer healthy mitochondria to HSC, facilitate HSC bioenergetics shift towards oxidative phosphorylation, and subsequently stimulate leukocyte expansion. Furthermore, metabolic rewiring following mitochondria transfer from HSPC to BM stromal cells likely to repair the damaged BM niche and accelerate limiting HSC transplantation post myeloablative conditioning.

综述目的:造血干细胞(HSC)和骨髓(BM)微环境之间建立了良好的串扰关系,这对于造血紧急情况下的稳态和造血再生至关重要。近十年来,细胞质和细胞器在细胞间的传递所介导的细胞间通讯可以使受损细胞再生和/或修复。线粒体最近被认为是造血干细胞命运的潜在调节因子。本文旨在讨论线粒体动力学的最新进展,特别是线粒体转移在维持HSC活性中的作用,并在干细胞移植和再生医学中具有明确的意义。最近研究发现:HSC的线粒体代谢具有高度异质性,其静止和效力取决于线粒体动力学状态和受损线粒体的清除。最近的证据表明,在应激反应中,BM间质细胞将健康的线粒体转移到HSC,促进HSC生物能量向氧化磷酸化转变,随后刺激白细胞扩张。此外,线粒体从造血干细胞转移到骨髓基质细胞后的代谢重连接可能会修复受损的骨髓生态位,并在清髓后加速限制造血干细胞移植。
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引用次数: 2
Biomechanical Regulation of Stem Cell Fate 干细胞命运的生物力学调控
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-03-01 DOI: 10.1007/s40778-020-00183-1
Linlin Jin, Ping Wang, Fang Ni
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引用次数: 0
Integration of mechanical and ECM microenvironment signals in the determination of cancer stem cell states. 机械和ECM微环境信号在肿瘤干细胞状态测定中的整合。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-03-01 Epub Date: 2020-11-23 DOI: 10.1007/s40778-020-00182-2
Tiina A Jokela, Mark A LaBarge

Purpose of review: Cancer stem cells (CSCs) are increasingly understood to play a central role in tumor progression. Growing evidence implicates tumor microenvironments as a source of signals that regulate or even impose CSC states on tumor cells. This review explores points of integration for microenvironment-derived signals that are thought to regulate CSCs in carcinomas.

Recent findings: CSC states are directly regulated by the mechanical properties and extra cellular matrix (ECM) composition of tumor microenvironments that promote CSC growth and survival, which may explain some modes of therapeutic resistance. CSCs sense mechanical forces and ECM composition through integrins and other cell surface receptors, which then activate a number of intracellular signaling pathways. The relevant signaling events are dynamic and context-dependent.

Summary: CSCs are thought to drive cancer metastases and therapeutic resistance. Cells that are in CSC states and more differentiated states appear to be reversible and conditional upon the components of the tumor microenvironment. Signals imposed by tumor microenvironment are of a combinatorial nature, ultimately representing the integration of multiple physical and chemical signals. Comprehensive understanding of the tumor microenvironment-imposed signaling that maintains cells in CSC states may guide future therapeutic interventions.

综述目的:肿瘤干细胞(CSCs)在肿瘤进展中发挥着核心作用。越来越多的证据表明,肿瘤微环境是调节甚至将CSC状态强加于肿瘤细胞的信号来源。这篇综述探讨了微环境来源信号的整合点,这些信号被认为在肿瘤中调节CSCs。最近的研究发现:肿瘤微环境的机械特性和细胞外基质(ECM)组成直接调节CSC状态,促进CSC生长和存活,这可能解释了某些治疗耐药模式。CSCs通过整合素和其他细胞表面受体感知机械力和ECM成分,然后激活许多细胞内信号通路。相关的信令事件是动态的,并且依赖于上下文。摘要:CSCs被认为驱动癌症转移和治疗耐药性。处于CSC状态和分化程度更高的细胞似乎是可逆的,并且取决于肿瘤微环境的组成部分。肿瘤微环境施加的信号具有组合性,最终表现为多种物理和化学信号的整合。全面了解维持细胞CSC状态的肿瘤微环境施加的信号传导可能指导未来的治疗干预。
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引用次数: 8
Cellular Complexity of Hemochorial Placenta: Stem Cell Populations, Insights from scRNA-seq, and SARS-CoV-2 Susceptibility. 止血胎盘的细胞复杂性:干细胞群体,scRNA-seq的见解和严重急性呼吸系统综合征冠状病毒2型易感性。
IF 2.3 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-01-01 Epub Date: 2021-10-20 DOI: 10.1007/s40778-021-00194-6
Christopher S Mallery, Maira Carrillo, Ariel Mei, Ana Correia-Branco, Olga Kashpur, Mary C Wallingford

Purpose of review: The placenta is a transient organ that forms de novo and serves a critical role in supporting fetal growth and development. Placental oxygen, nutrients, and waste are transported through processes that depend on vascular structure and cell type-specific expression and localization of membrane transporters. Understanding how the placenta develops holds great significance for maternal-fetal medicine. The purpose of this review is to examine current information regarding placental progenitor populations.

Recent findings: Recent advancements in single-cell RNA sequencing (scRNA-seq) provide unprecedented depth for the investigation of cell type-specific gene expression patterns in the placenta. Thus far, several mouse placenta scRNA-seq studies have been conducted which produced and analyzed transcriptomes of placental progenitors and cells of the fully developed placenta between embryonic day (E) 7.0 and E12.5. Together with human placenta scRNA-seq data which, in part, has been produced through coordinated research campaigns in the scientific community to understand the potential for SARS-CoV-2 infection, these mammalian studies lend fundamental insight into the cellular and molecular composition of hemochorial placentae found in both mouse and human.

Summary: Single-cell placenta research has advanced understanding of tissue-resident stem cells and molecules that are poised to support maternal-fetal communication and nutrient transport. Herein, we provide context for these recent findings by reviewing placental anatomy and cell populations, and discuss recent scRNA-seq mouse placenta findings. Further research is needed to evaluate the utility of placental stem cells in the development of new therapeutic approaches for the treatment of wound healing and disease.

综述目的:胎盘是一种新形成的短暂器官,在支持胎儿生长发育方面发挥着关键作用。胎盘的氧气、营养物质和废物通过依赖于血管结构和细胞类型特异性表达和膜转运蛋白定位的过程进行运输。了解胎盘是如何发育的,对母婴医学具有重要意义。这篇综述的目的是检查有关胎盘祖细胞群体的最新信息。最近的发现:单细胞RNA测序(scRNA-seq)的最新进展为研究胎盘中细胞类型特异性基因表达模式提供了前所未有的深度。到目前为止,已经进行了几项小鼠胎盘scRNA-seq研究,这些研究产生并分析了胚胎期(E)7.0和E12.5之间完全发育的胎盘的胎盘祖细胞和细胞的转录组。再加上人类胎盘scRNA-seq数据,这些数据在一定程度上是通过科学界的协调研究活动产生的,以了解严重急性呼吸系统综合征冠状病毒2型感染的可能性,这些哺乳动物研究为深入了解小鼠和人类血系胎盘的细胞和分子组成提供了基础。摘要:单细胞胎盘研究对支持母婴沟通和营养运输的组织驻留干细胞和分子有了深入的了解。在此,我们通过回顾胎盘解剖结构和细胞群,为这些最新发现提供了背景,并讨论了scRNA-seq小鼠胎盘的最新发现。需要进一步的研究来评估胎盘干细胞在开发治疗伤口愈合和疾病的新治疗方法中的效用。
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引用次数: 0
Preclinical Studies and Clinical Prospects of Wharton's Jelly-Derived MSC for Treatment of Acute Radiation Syndrome. 沃顿果冻源MSC治疗急性放射综合征的临床前研究和临床前景。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2021-01-01 Epub Date: 2021-04-28 DOI: 10.1007/s40778-021-00188-4
Mayuri Bandekar, Dharmendra K Maurya, Deepak Sharma, Santosh K Sandur

Purpose of review: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have received widespread attention from researchers owing to the remarkable benefits offered by these cells over other stem cells. The primitive nature of WJ-MSCs, ease of isolation, differentiation ability, and immuno-modulatory nature make these cells superior to bone marrow MSCs and ideal to treat various human ailments. This review explores ability of WJ-MSCs to mitigate acute radiation syndrome caused by planned or unplanned radiation exposure.

Recent findings: Recent reports suggest that WJ-MSCs home to damaged tissues in irradiated host and mitigate radiation induced damage to radiosensitive tissues such as hematopoietic and gastrointestinal systems. WJ-MSCs and conditioned media were found to protect mice from radiation induced mortality and also prevent radiation dermatitis. Local irradiation-induced lung toxicity in mice was significantly reduced by CXCR4 over-expressing WJ-MSCs.

Summary: Emerging evidences support safety and effectiveness of WJ-MSCs for treatment of acute radiation syndrome and lung injury after planned or accidental exposure. Additionally, conditioned media collected after culturing WJ-MSCs can also be used for mitigation of radiation dermatitis. Clinical translation of these findings would be possible after careful evaluation of resilience, effectiveness, and molecular mechanism of action of xenogeneic WJ-MSCs in non-human primates.

综述目的:Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs)由于其与其他干细胞相比具有显著的益处而受到了研究人员的广泛关注。WJ-MSCs的原始性质、易于分离、分化能力和免疫调节性质使这些细胞优于骨髓MSCs,是治疗各种人类疾病的理想选择。本文探讨WJ-MSCs减轻计划或计划外辐射暴露引起的急性辐射综合征的能力。最近的研究发现:最近的报道表明,WJ-MSCs可以在受辐射的宿主中修复受损组织,并减轻辐射引起的对辐射敏感组织(如造血和胃肠道系统)的损伤。发现WJ-MSCs和条件培养基具有保护小鼠免受辐射致死和预防放射性皮炎的作用。过表达CXCR4的WJ-MSCs可显著降低小鼠局部辐射诱导的肺毒性。总结:新出现的证据支持WJ-MSCs治疗急性辐射综合征和计划或意外暴露后肺损伤的安全性和有效性。此外,培养WJ-MSCs后收集的条件培养基也可用于缓解放射性皮炎。在仔细评估异种WJ-MSCs在非人灵长类动物中的恢复力、有效性和分子作用机制后,这些发现的临床转化将是可能的。
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引用次数: 3
Hematopoietic Stem Cell Stress and Regeneration 造血干细胞应激与再生
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-12-01 DOI: 10.1007/s40778-020-00181-3
C. Termini, J. Chute
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引用次数: 2
The role of RNA epigenetic modification in normal and malignant hematopoiesis. RNA表观遗传修饰在正常和恶性造血中的作用。
IF 1.4 Q4 CELL & TISSUE ENGINEERING Pub Date : 2020-12-01 Epub Date: 2020-08-12 DOI: 10.1007/s40778-020-00178-y
Radovan Vasic, Yimeng Gao, Chengyang Liu, Stephanie Halene

Purpose of review: RNA epigenetic modifications have been identified as novel, dynamic regulators of gene expression, with important impacts on stem cell fate decisions. Here we examine the functions of RNA modifications, with a focus on N 6-methyladenosine (m6A), in hematopoietic stem cells under normal conditions and in malignancy.

Recent findings: The m6A RNA modification is a critical regulator of hematopoiesis. Disruption of different elements of the m6A machinery can skew the balance of self-renewal and differentiation in normal hematopoietic stem cells. The m6A reader, writer, and eraser proteins are also overexpressed in myeloid leukemia, and disruption of their function impairs leukemogenesis. RNA m6A modification governs important aspects of immune system function, including immune cell development, immune signaling, and recognition of RNA as foreign or self. In hematopoietic stem cells, endogenously-derived double stranded RNA can form in the absence of m6A, inducing deleterious inflammatory pathways which compromise stem cell function.

Summary: The RNA modification m6A exerts a variety of functions in normal hematopoietic stem cells as well as leukemic cells. Pharmacologic modulation of different elements of the m6A machinery provides a promising avenue for ex vivo expansion of hematopoietic stem cells in the transplant setting, as well as for leukemia therapy.

综述目的:RNA表观遗传修饰被认为是一种新的、动态的基因表达调节因子,对干细胞的命运决定具有重要影响。在这里,我们研究了RNA修饰的功能,重点是n6 -甲基腺苷(m6A),在正常条件下和恶性造血干细胞。最近的研究发现:m6A RNA修饰是造血的关键调节因子。破坏m6A机制的不同元素可以扭曲正常造血干细胞自我更新和分化的平衡。m6A读取器、写入器和擦除器蛋白也在髓性白血病中过度表达,其功能的破坏会损害白血病的发生。RNA m6A修饰控制着免疫系统功能的重要方面,包括免疫细胞发育、免疫信号传导和对外来或自身RNA的识别。在造血干细胞中,内源性衍生的双链RNA可以在缺乏m6A的情况下形成,诱导有害的炎症途径,损害干细胞的功能。摘要:RNA修饰m6A在正常造血干细胞和白血病细胞中发挥多种功能。m6A机制中不同元素的药理学调节为造血干细胞在移植环境中的体外扩增以及白血病治疗提供了一条有希望的途径。
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引用次数: 10
期刊
Current Stem Cell Reports
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