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Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells. 神经酸抑制人华顿果冻来源的间充质干细胞的复制衰老。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-12 DOI: 10.15283/ijsc23101
Sun Jeong Kim, Soojin Kwon, Soobeen Chung, Eun Joo Lee, Sang Eon Park, Suk-Joo Choi, Soo-Young Oh, Gyu Ha Ryu, Hong Bae Jeon, Jong Wook Chang

Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated β-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

细胞衰老导致细胞周期停滞,并促进增殖的永久停止。由于间充质干细胞(MSC)的衰老降低了增殖和多能性并增加了免疫原性,因此老化的MSC不适合细胞治疗。因此,抑制MSCs细胞衰老具有重要意义。最近有报道称,代谢产物可以控制衰老疾病。因此,我们旨在鉴定调节骨髓间充质干细胞复制衰老的新代谢产物。利用粪便代谢产物库,我们确定神经酸(NA)是复制衰老调控的候选代谢产物。在复制性衰老MSCs中,NA降低了衰老相关的β-半乳糖苷酶阳性细胞、衰老相关基因的表达,并增加了干性和脂肪生成。此外,在非衰老的MSCs中,NA处理延缓了顺序传代引起的衰老,并促进了增殖。我们首次证实,NA延缓并抑制细胞衰老。考虑到药物治疗的最佳浓度、持续时间和时间,NA是一种新的潜在代谢产物,可用于开发调节细胞衰老的技术。
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引用次数: 0
Integrin α4 Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced Engraftment into Myocardial Infarction. 脂肪来源干细胞中整合素α4阳性亚群通过增强植入心肌梗死有效减少梗死面积。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-19 DOI: 10.15283/ijsc22209
Zihui Yuan, Juan Tan, Jian Wang

The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin α4, limiting their homing capacity. This study aims to characterize integrin α4 ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin α4 ASCs subpopulation, which were characterized in vitro and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin α4 ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin α4 receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α4 ASCs subpopulation into the 3-day infarcted myocardium. Integrin α4 ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α4 ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α4 ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.

脂肪来源干细胞(ASCs)治疗心肌梗死的疗效因存活率和植入率低而受到限制。整合素介导的细胞粘附是其存活和归巢的先决条件。ASCs表达的整合素α4不足,限制了其归巢能力。本研究旨在鉴定整合素α4+ASC亚群,并探讨其对心肌梗死的治疗作用。我们使用荧光激活细胞分选来获得整合素α4+ASCs亚群,这些亚群在体外进行了表征并移植到心肌梗死模型中。进行正电子发射断层扫描成像来测量梗死的大小。心脏电影磁共振成像用于评估心脏收缩功能。与未分化的ASCs相比,整合素α4+ASCs亚群分泌更高水平的血管生成生长因子,迁移更快,并表现出更强的抗凋亡能力。心肌梗死后第3天,血管细胞粘附分子-1明显上调,与ASCs表面的整合素α4受体相互作用,提高其存活率和粘附力。因此,我们将未分化的ASCs或整合素α4+ASCs亚群植入梗死3天的心肌中。整合素α4+ASCs亚群在梗死心肌中表现出更强的植入能力。整合素α4+ASCs亚群比未分级的ASCs更有效地缩小梗死面积并加强心功能恢复。在动物模型中,整合素α4+ASCs亚群在改善缺血性心肌损伤方面优于未分级的ASCs。从机制上讲,它们更牢固地植入梗死区,更高的迁移能力和旁分泌因子的释放增加有助于增强组织修复。
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引用次数: 0
Unleashing the Power of Undifferentiated Induced Pluripotent Stem Cell Bioprinting: Current Progress and Future Prospects. 释放未分化诱导多能干细胞生物打印的力量:当前进展与未来展望》。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2024-01-02 DOI: 10.15283/ijsc23146
Boyoung Kim, Jiyoon Kim, Soah Lee

Induced pluripotent stem cell (iPSC) technology has revolutionized various fields, including stem cell research, disease modeling, and regenerative medicine. The evolution of iPSC-based models has transitioned from conventional two-dimensional systems to more physiologically relevant three-dimensional (3D) models such as spheroids and organoids. Nonetheless, there still remain challenges including limitations in creating complex 3D tissue geometry and structures, the emergence of necrotic core in existing 3D models, and limited scalability and reproducibility. 3D bioprinting has emerged as a revolutionary technology that can facilitate the development of complex 3D tissues and organs with high scalability and reproducibility. This innovative approach has the potential to effectively bridge the gap between conventional iPSC models and complex 3D tissues in vivo. This review focuses on current trends and advancements in the bioprinting of iPSCs. Specifically, it covers the fundamental concepts and techniques of bioprinting and bioink design, reviews recent progress in iPSC bioprinting research with a specific focus on bioprinting undifferentiated iPSCs, and concludes by discussing existing limitations and future prospects.

诱导多能干细胞(iPSC)技术给干细胞研究、疾病建模和再生医学等多个领域带来了革命性的变化。基于iPSC的模型已从传统的二维系统发展到更贴近生理的三维(3D)模型,如球体和有机体。然而,挑战依然存在,包括创建复杂三维组织几何形状和结构的局限性、现有三维模型出现坏死核心以及可扩展性和可重复性有限。三维生物打印已成为一项革命性技术,可促进复杂三维组织和器官的发展,并具有高度的可扩展性和可重复性。这种创新方法有望有效弥合传统 iPSC 模型与体内复杂三维组织之间的差距。本综述重点介绍 iPSCs 生物打印的当前趋势和进展。具体而言,它涵盖了生物打印和生物墨水设计的基本概念和技术,回顾了 iPSC 生物打印研究的最新进展,特别关注未分化 iPSC 的生物打印,最后讨论了现有限制和未来前景。
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引用次数: 0
Expression of Major Histocompatibility Complex during Neuronal Differentiation of Somatic Cell Nuclear Transfer-Human Embryonic Stem Cells. 主要组织相容性复合体在体细胞核移植人胚胎干细胞神经元分化过程中的表达。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-26 DOI: 10.15283/ijsc23037
Jin Saem Lee, Jeoung Eun Lee, Shin-Hye Yu, Taehoon Chun, Mi-Yoon Chang, Dong Ryul Lee, Chang-Hwan Park

Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

人类多能干细胞(hPSC),如人类胚胎干细胞(hESCs)、诱导多能干细胞和体细胞核转移(SCNT)-hESCs可以永久自我更新,同时保持其分化为任何类型体细胞的能力,从而成为细胞治疗的重要细胞源。然而,hPSCs在临床试验中的应用存在持续的挑战,其中最重要的挑战之一是当从异基因(非自身)细胞源获得移植时,患者免疫系统对人类白细胞抗原(HLA)错配的反应引起的移植物排斥。使用纯合的SCNT-hESCs(homo-SCNT-hESC)来简化临床应用并减少HLA错配。在这里,我们提出了一种无外源性方案,该方案证实了hPSCs中神经前体细胞的有效生成以及多巴胺能神经元的分化。此外,当比较hESC、同源SCNT-hESCs和异源SCNT-hESC的HLA表达模式时没有差异。我们提出,在体外培养的hPSCs之间,分化能力和HLA表达没有差异。因此,在临床试验中,当与神经前体细胞一起移植时,预计同源SCNT-hESCs将具有更广泛的应用。
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引用次数: 0
Lung Organoid on a Chip: A New Ensemble Model for Preclinical Studies. 芯片上的肺类器官:一种用于临床前研究的新集合模型。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-11 DOI: 10.15283/ijsc23090
Hyung-Jun Kim, Sohyun Park, Seonghyeon Jeong, Jihoon Kim, Young-Jae Cho

The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.

肺是一个复杂的器官,包括连接大气道和数百万个末端气体交换单元的分支气道。使用细胞系模型系统进行的传统肺部生物医学研究具有局限性,如缺乏细胞异质性,动物模型也存在局限性,包括伦理问题、种族差异和体内生理差异。类有机物和片上模型为这些问题提供了可行的解决方案。类器官是一种三维的自组织结构,由大量来源于干细胞的细胞组成,干细胞与维持干细胞所需的生长因子一起培养。芯片上模型是仿生微系统,能够定制使用微流体系统来模拟血液通道中的血液流动或真空来模拟人类呼吸。这篇综述总结了肺类器官和肺片上模型的关键组成部分和以往的生物医学研究,并介绍了潜在的未来应用。考虑到这些模型系统的重要性和益处,我们相信该系统将为肺部疾病的生物医学研究人员提供更好的平台,如新出现的病毒感染、进行性纤维化肺部疾病或原发性或转移性癌症。
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引用次数: 0
Exploring the Molecular and Developmental Dynamics of Endothelial Cell Differentiation. 探讨内皮细胞分化的分子和发育动力学。
IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-26 DOI: 10.15283/ijsc23086
Yu Jung Shin, Jung Hyun Lee

The development and differentiation of endothelial cells (ECs) are fundamental processes with significant implications for both health and disease. ECs, which are found in all organs and blood vessels, play a crucial role in facilitating nutrient and waste exchange and maintaining proper vessel function. Understanding the intricate signaling pathways involved in EC development holds great promise for enhancing vascularization, tissue engineering, and vascular regeneration. Hematopoietic stem cells originating from hemogenic ECs, give rise to diverse immune cell populations, and the interaction between ECs and immune cells is vital for maintaining vascular integrity and regulating immune responses. Dysregulation of vascular development pathways can lead to various diseases, including cancer, where tumor-specific ECs promote tumor growth through angiogenesis. Recent advancements in single-cell genomics and in vivo genetic labeling have shed light on EC development, plasticity, and heterogeneity, uncovering tissue-specific gene expression and crucial signaling pathways. This review explores the potential of ECs in various applications, presenting novel opportunities for advancing vascular medicine and treatment strategies.

内皮细胞(EC)的发育和分化是对健康和疾病都有重要意义的基本过程。内皮细胞存在于所有器官和血管中,在促进营养和废物交换以及维持适当的血管功能方面发挥着至关重要的作用。了解EC发育中涉及的复杂信号通路对增强血管形成、组织工程和血管再生具有很大的前景。源自造血内皮细胞的造血干细胞产生不同的免疫细胞群,内皮细胞和免疫细胞之间的相互作用对于维持血管完整性和调节免疫反应至关重要。血管发育途径的失调可导致多种疾病,包括癌症,其中肿瘤特异性EC通过血管生成促进肿瘤生长。单细胞基因组学和体内基因标记的最新进展揭示了EC的发展、可塑性和异质性,揭示了组织特异性基因表达和关键的信号通路。这篇综述探讨了内皮细胞在各种应用中的潜力,为推进血管医学和治疗策略提供了新的机会。
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引用次数: 0
Recent Research Trends in Stem Cells Using CRISPR/Cas-Based Genome Editing Methods. 基于CRISPR/Cas的基因组编辑方法在干细胞中的最新研究趋势。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-10-31 DOI: 10.15283/ijsc23030
Da Eun Yoon, Hyunji Lee, Kyoungmi Kim

The clustered regularly interspaced short palindromic repeats (CRISPR) system, a rapidly advancing genome editing technology, allows DNA alterations into the genome of organisms. Gene editing using the CRISPR system enables more precise and diverse editing, such as single nucleotide conversion, precise knock-in of target sequences or genes, chromosomal rearrangement, or gene disruption by simple cutting. Moreover, CRISPR systems comprising transcriptional activators/repressors can be used for epigenetic regulation without DNA damage. Stem cell DNA engineering based on gene editing tools has enormous potential to provide clues regarding the pathogenesis of diseases and to study the mechanisms and treatments of incurable diseases. Here, we review the latest trends in stem cell research using various CRISPR/Cas technologies and discuss their future prospects in treating various diseases.

聚集的规则间隔短回文重复序列(CRISPR)系统是一种快速发展的基因组编辑技术,可以使DNA改变到生物体的基因组中。使用CRISPR系统的基因编辑能够实现更精确和多样化的编辑,例如单核苷酸转换、靶序列或基因的精确敲除、染色体重排或通过简单切割的基因破坏。此外,包含转录激活剂/阻遏物的CRISPR系统可用于表观遗传学调控而不会对DNA造成损伤。基于基因编辑工具的干细胞DNA工程具有巨大的潜力,可以为疾病的发病机制提供线索,并研究不治之症的机制和治疗方法。在这里,我们回顾了使用各种CRISPR/Cas技术进行干细胞研究的最新趋势,并讨论了它们在治疗各种疾病方面的未来前景。
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引用次数: 0
Mimicking the Human Articular Joint with In Vitro Model of Neurons-Synoviocytes Co-Culture. 神经元-滑膜细胞体外共培养模拟人关节模型。
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-02-28 Epub Date: 2023-11-24 DOI: 10.15283/ijsc23043
Jakub Chwastek, Marta Kędziora, Małgorzata Borczyk, Michał Korostyński, Katarzyna Starowicz

The development of in vitro models is essential in modern science due to the need for experiments using human material and the reduction in the number of laboratory animals. The complexity of the interactions that occur in living organisms requires improvements in the monolayer cultures. In the work presented here, neuroepithelial stem (NES) cells were differentiated into peripheral-like neurons (PLN) and the phenotype of the cells was confirmed at the genetic and protein levels. Then RNA-seq method was used to investigate how stimulation with pro-inflammatory factors such as LPS and IFNγ affects the expression of genes involved in the immune response in human fibroblast-like synoviocytes (HFLS). HFLS were then cultured on semi-permeable membrane inserts, and after 24 hours of pro-inflammatory stimulation, the levels of cytokines secretion into the medium were checked. Inserts with stimulated HFLS were introduced into the PLN culture, and by measuring secreted ATP, an increase in cell activity was found in the system. The method used mimics the condition that occurs in the joint during inflammation, as observed in the development of diseases such as rheumatoid arthritis (RA) or osteoarthritis (OA). In addition, the system used can be easily modified to simulate the interaction of peripheral neurons with other cell types.

由于需要使用人体材料进行实验和实验动物数量的减少,体外模型的发展在现代科学中是必不可少的。生物体内发生的相互作用的复杂性要求对单层培养进行改进。在这里的工作中,神经上皮干细胞(NES)分化为外周样神经元(PLN),并在遗传和蛋白质水平上证实了细胞的表型。然后采用RNA-seq方法研究促炎因子(如LPS和IFNγ)刺激如何影响人成纤维细胞样滑膜细胞(HFLS)免疫应答相关基因的表达。然后将HFLS培养在半透膜插入物上,促炎刺激24小时后,检测培养基中细胞因子的分泌水平。将刺激HFLS的插入物引入PLN培养,通过测量分泌的ATP,发现系统中细胞活性增加。所使用的方法模拟炎症期间发生在关节中的情况,如在类风湿关节炎(RA)或骨关节炎(OA)等疾病的发展中观察到的情况。此外,所使用的系统可以很容易地修改,以模拟周围神经元与其他细胞类型的相互作用。
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引用次数: 0
Immune-Epithelial Cell Interactions during Epidermal Regeneration, Repair, and Inflammatory Diseases. 表皮再生、修复和炎症性疾病过程中免疫与上皮细胞的相互作用
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2024-01-09 DOI: 10.15283/ijsc23107
Axel D Schmitter-Sánchez, Sangbum Park

The multiple layers of the skin cover and protect our entire body. Among the skin layers, the epidermis is in direct contact with the outer environment and serves as the first line of defense. The epidermis functions as a physical and immunological barrier. To maintain barrier function, the epidermis continually regenerates and repairs itself when injured. Interactions between tissue-resident immune cells and epithelial cells are essential to sustain epidermal regeneration and repair. In this review, we will dissect the crosstalk between epithelial cells and specific immune cell populations located in the epidermis during homeostasis and wound repair. In addition, we will analyze the contribution of dysregulated immune-epithelial interactions in chronic inflammatory diseases.

多层皮肤覆盖并保护着我们的全身。在皮肤层中,表皮直接与外界环境接触,是第一道防线。表皮起着物理和免疫屏障的作用。为了保持屏障功能,表皮会不断再生,并在受伤时进行自我修复。组织驻留免疫细胞和上皮细胞之间的相互作用对维持表皮再生和修复至关重要。在这篇综述中,我们将剖析上皮细胞和位于表皮的特定免疫细胞群在平衡和伤口修复过程中的相互作用。此外,我们还将分析免疫-表皮相互作用失调在慢性炎症性疾病中的作用。
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引用次数: 0
Host-Microbe Interactions Regulate Intestinal Stem Cells and Tissue Turnover in Drosophila. 宿主-微生物相互作用调控果蝇的肠干细胞和组织转换
IF 2.3 4区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2023-12-21 DOI: 10.15283/ijsc23172
Ji-Hoon Lee
With the activity of intestinal stem cells and continuous turnover, the gut epithelium is one of the most dynamic tissues in animals. Due to its simple yet conserved tissue structure and enteric cell composition as well as advanced genetic and histologic techniques, Drosophila serves as a valuable model system for investigating the regulation of intestinal stem cells. The Drosophila gut epithelium is in constant contact with indigenous microbiota and encounters externally introduced "non-self" substances, including foodborne pathogens. Therefore, in addition to its role in digestion and nutrient absorption, another essential function of the gut epithelium is to control the expansion of microbes while maintaining its structural integrity, necessitating a tissue turnover process involving intestinal stem cell activity. As a result, the microbiome and pathogens serve as important factors in regulating intestinal tissue turnover. In this manuscript, I discuss crucial discoveries revealing the interaction between gut microbes and the host's innate immune system, closely associated with the regulation of intestinal stem cell proliferation and differentiation, ultimately contributing to epithelial homeostasis.
由于肠道干细胞的活性和不断更替,肠道上皮细胞是动物体内最具活力的组织之一。由于果蝇的组织结构和肠道细胞组成简单而保守,加上先进的遗传学和组织学技术,果蝇成为研究肠道干细胞调控的宝贵模型系统。果蝇的肠道上皮细胞不断与本地微生物群接触,并遇到外部引入的 "非自身 "物质,包括食源性病原体。因此,除了在消化和营养吸收方面的作用外,肠道上皮的另一个基本功能是控制微生物的扩张,同时保持其结构的完整性,这就需要一个涉及肠道干细胞活动的组织更替过程。因此,微生物组和病原体是调节肠道组织更替的重要因素。在这篇手稿中,我讨论了揭示肠道微生物与宿主先天性免疫系统之间相互作用的重要发现,这种相互作用与肠道干细胞增殖和分化的调节密切相关,最终有助于上皮细胞的稳态。
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引用次数: 0
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International journal of stem cells
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