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Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis. 间充质基质/干细胞疗法在临床前体内模型中改善辐射诱发的唾液腺功能减退的唾液流速:系统综述与元分析》。
IF 4.5 3区 医学 Q2 CELL & TISSUE ENGINEERING Pub Date : 2024-05-01 Epub Date: 2024-03-02 DOI: 10.1007/s12015-024-10700-y
Amanda-Louise Fenger Carlander, Anders Kierkegaard Gundestrup, Per Marcus Jansson, Bjarke Follin, Cecilie Hoeeg, Birgitte Saima Kousholt, Rasmus Tolstrup Larsen, Kathrine Kronberg Jakobsen, Susie Rimborg, Anne Fischer-Nielsen, Christian Grønhøj, Christian von Buchwald, Charlotte Duch Lynggaard

Background: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies.

Methods: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336.

Results: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors.

Conclusion: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.

背景:间充质基质/干细胞(MSCs)被认为可用于放射性诱导的唾液腺损伤后的唾液腺(SG)修复。本研究旨在确定间充质干细胞疗法在临床前体内研究中对放射性诱导的唾液腺损伤和功能低下的安全性和有效性:方法:系统检索了 PubMed 和 EMBASE 上 2022 年 1 月 10 日之前发表的临床前体内介入研究,这些研究评估了间充质干细胞治疗放射性诱导唾液腺损伤的有效性和安全性。主要终点是荟萃分析中评估的唾液流量(SFR)。研究方案已在 PROSPERO ( www.crd.ac.uk/prospero ) 上公布和注册,注册号为 CRD42021227336。结果:定性分析共纳入了 16 项临床前体内研究(858 只实验动物),荟萃分析共纳入了 13 项临床前体内研究(404 只实验动物)。间充质干细胞来源于骨髓(4 项研究)、脂肪组织(10 项研究)和唾液腺组织(2 项研究),给药方式为静脉注射(3 项研究)、腺内注射(11 项研究)或皮下注射(1 项研究)。无严重不良事件报告。对 SFR 的总体疗效显著提高,标准化平均差 (SMD) 为 6.99(95% CI:2.55-11.42)。研究报告显示,尖锐湿疣组织、血管面积和旁分泌因子均有所改善:总之,该系统综述和荟萃分析表明,在临床前体内研究中,间充质干细胞疗法对放疗后SG功能恢复和SG组织再生有显著效果,且无严重不良反应。间充质干细胞疗法在治疗放疗引起的口腔干燥症方面具有巨大的治疗潜力,但要确定其在临床环境中的疗效,还需要进行全面、随机的人体临床试验。
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引用次数: 0
Enhancing Vasculogenesis in Dental Pulp Development: DPSCs-ECs Communication via FN1-ITGA5 Signaling. 增强牙髓发育过程中的血管生成:通过 FN1-ITGA5 信号传递的 DPSCs-ECs 通信
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-05-01 Epub Date: 2024-02-28 DOI: 10.1007/s12015-024-10695-6
Tiankai Di, Chao Feng, Lulu Wang, Jinlong Xu, Yang Du, Baixiang Cheng, Yujiang Chen, Lian Wu

Background: Dental pulp regeneration therapy is a challenge to achieve early vascularization during treatment. Studying the regulatory mechanisms of vascular formation during human dental pulp development may provide insights for related therapies. In this study, we utilized single-cell sequencing analysis to compare the gene expression of dental pulp stem cells (DPSCs) and vascular endothelial cells (ECs) from developing and mature dental pulps.

Method: Immunohistochemistry, Western blot, and real-time polymerase chain reaction (RT-PCR) were used to detect fibronectin 1 (FN1) expression and molecules, such as PI3K/AKT. Cell proliferation assay, scratch assay, tube formation assay and were used to investigate the effects of DPSCs on the vasculogenetic capability of ECs. Additionally, animal experiments involving mice were conducted.

Result: The results revealed that DPSCs exist around dental pulp vasculature. FN1 expression was significantly higher in DPSCs from young permanent pulps than mature pulps, promoting HUVEC proliferation, migration, and tube formation via ITGA5 and the downstream PI3K/AKT signaling pathway.

Conclusion: Our data indicate that intercellular communication between DPSCs and ECs mediated by FN1-ITGA5 signaling is crucial for vascularizationduring dental pulp development, laying an experimental foundation for future clinical studies.

背景:牙髓再生疗法在治疗过程中实现早期血管化是一项挑战。研究人类牙髓发育过程中血管形成的调控机制可为相关疗法提供启示。在这项研究中,我们利用单细胞测序分析比较了发育中和成熟牙髓的牙髓干细胞(DPSCs)和血管内皮细胞(ECs)的基因表达:免疫组化、Western印迹和实时聚合酶链反应(RT-PCR)用于检测纤连蛋白1(FN1)和PI3K/AKT等分子的表达。细胞增殖试验、划痕试验、管形成试验等被用来研究 DPSCs 对 ECs 血管生成能力的影响。此外,还进行了小鼠动物实验:结果:研究结果显示,牙髓血管周围存在 DPSCs。FN1在年轻恒牙牙髓的DPSCs中的表达明显高于成熟牙髓,通过ITGA5和下游的PI3K/AKT信号通路促进HUVEC的增殖、迁移和管形成:我们的数据表明,在牙髓发育过程中,由 FN1-ITGA5 信号传导介导的 DPSCs 和 ECs 之间的细胞间通信对血管化至关重要,这为未来的临床研究奠定了实验基础。
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引用次数: 0
The Evolutionary Route of in vitro Human Spermatogenesis: What is the Next Destination? 体外人类精子发生的进化路线:下一个目的地是哪里?
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-29 DOI: 10.1007/s12015-024-10726-2
Merve Gizer, Selin Önen, Petek Korkusuz

Malfunction in spermatogenesis due to genetic diseases, trauma, congenital disorders or gonadotoxic treatments results in infertility in approximately 7% of males. The behavior of spermatogonial stem cells (SSCs) within three-dimensional, multifactorial, and dynamic microenvironment implicates a niche that serves as a repository for fertility, since can serve as a source of mature and functional male germ cells. Current protocols enable reprogramming of mature somatic cells into induced pluripotent stem cells (iPSCs) and their limited differentiation to SSCs within the range of 0–5%. However, the resulting human iPSC-derived haploid spermatogenic germ cell yield in terms of number and functionality is currently insufficient for transfer to infertility clinic as a therapeutic tool. In this article, we reviewed the evolution of experimental culture platforms and introduced a novel iPSCs-based approach for in vitro spermatogenesis based on a niche perspective bearing cellular, chemical, and physical factors that provide the complex arrangement of testicular seminiferous tubules embedded within a vascularized stroma. We believe that bioengineered organoids supported by smart bio-printed tubules and microfluidic organ-on-a-chip systems offer efficient, precise, personalized platforms for autologous pluripotent stem cell sources to undergo the spermatogenetic cycle, presenting a promising tool for infertile male patients with complete testicular aplasia.

Graphical Abstract

由于遗传疾病、创伤、先天性疾病或性腺毒性治疗导致的精子发生功能障碍,导致约7%的男性不育。精原干细胞(SSCs)在三维、多因素和动态微环境中的行为表明,精原干细胞可以作为成熟和功能性男性生殖细胞的来源,是生育力的储存库。目前的方案可将成熟的体细胞重编程为诱导多能干细胞(iPSCs),并将其有限分化为 SSCs,分化率在 0-5% 之间。然而,由此产生的人类 iPSC 衍生的单倍体精原生殖细胞在数量和功能方面目前还不足以作为治疗工具应用于不孕不育临床。在这篇文章中,我们回顾了实验培养平台的演变,并介绍了一种基于 iPSCs 的体外精子发生新方法,该方法从生态位角度出发,包含细胞、化学和物理因素,提供了嵌入血管基质中的睾丸曲细精管的复杂排列。我们认为,由智能生物打印小管和微流控芯片器官系统支持的生物工程器官组织为自体多能干细胞源提供了高效、精确和个性化的平台,使其能够经历精子发生周期,为患有完全性睾丸发育不全的男性不育患者提供了一种前景广阔的工具。
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引用次数: 0
Delivery of Stem Cells and BMP-2 With Functionalized Self-Assembling Peptide Enhances Regeneration of Infarcted Myocardium. 用功能化自组装肽输送干细胞和 BMP-2 可促进梗死心肌的再生
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-24 DOI: 10.1007/s12015-024-10721-7
Hai-dong Guo, Jin-hong Wu, Hai-jie Wang, Yu-Zhen Tan
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引用次数: 0
PGE2 Overexpressing Human Embryonic Stem Cell Derived Mesenchymal Stromal Cell Relieves Liver Fibrosis in an Immuno-suppressive Manner. 过表达 PGE2 的人胚胎干细胞衍生间充质基质细胞以免疫抑制方式缓解肝纤维化
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-23 DOI: 10.1007/s12015-024-10728-0
Yan Zhong, Xiaohao Hu, Jingfeng Liu
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引用次数: 0
Base Editors-Mediated Gene Therapy in Hematopoietic Stem Cells for Hematologic Diseases. 基地编辑--造血干细胞基因治疗血液病。
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-22 DOI: 10.1007/s12015-024-10715-5
Chengpeng Zhang, Jinchao Xu, Yikang Wu, Can Xu, Peng Xu
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引用次数: 0
Replacing Animal Testing with Stem Cell-Organoids : Advantages and Limitations 用干细胞-有机物取代动物试验:优势与局限性
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-19 DOI: 10.1007/s12015-024-10723-5
Guiyoung Park, Yeri Alice Rim, Yeowon Sohn, Yoojun Nam, Ji Hyeon Ju

Various groups including animal protection organizations, medical organizations, research centers, and even federal agencies such as the U.S. Food and Drug Administration, are working to minimize animal use in scientific experiments. This movement primarily stems from animal welfare and ethical concerns. However, recent advances in technology and new studies in medicine have contributed to an increase in animal experiments throughout the years. With the rapid increase in animal testing, concerns arise including ethical issues, high cost, complex procedures, and potential inaccuracies.

Alternative solutions have recently been investigated to address the problems of animal testing. Some of these technologies are related to stem cell technologies, such as organ-on-a-chip, organoids, and induced pluripotent stem cell models. The aim of the review is to focus on stem cell related methodologies, such as organoids, that can serve as an alternative to animal testing and discuss its advantages and limitations, alongside regulatory considerations.

Although stem cell related methodologies has shortcomings, it has potential to replace animal testing. Achieving this requires further research on stem cells, with potential societal and technological benefits.

Graphical Abstract

包括动物保护组织、医疗组织、研究中心,甚至美国食品和药物管理局等联邦机构在内的各种团体都在努力减少科学实验中的动物使用。这一运动主要源于对动物福利和伦理的担忧。然而,近年来技术的进步和医学领域的新研究也导致了动物实验的增加。随着动物实验的迅速增加,人们开始关注包括伦理问题、高成本、复杂的程序和潜在的不准确性等问题。其中一些技术与干细胞技术有关,如芯片器官、器官组织和诱导多能干细胞模型。本综述旨在重点介绍干细胞相关方法,如有机体,这些方法可替代动物实验,并讨论其优势和局限性,以及监管方面的考虑。要实现这一目标,需要对干细胞进行进一步研究,以获得潜在的社会和技术利益。
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引用次数: 0
The Endometrial Stem/Progenitor Cells and Their Niches 子宫内膜干细胞/祖细胞及其位置
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-18 DOI: 10.1007/s12015-024-10725-3
Baolan Sun, Xi Cheng, Qiang Wu

Endometrial stem/progenitor cells are a type of stem cells with the ability to self-renew and differentiate into multiple cell types. They exist in the endometrium and form niches with their neighbor cells and extracellular matrix. The interaction between endometrial stem/progenitor cells and niches plays an important role in maintaining, repairing, and regenerating the endometrial structure and function. This review will discuss the characteristics and functions of endometrial stem/progenitor cells and their niches, the mechanisms of their interaction, and their roles in endometrial regeneration and diseases. Finally, the prospects for their applications will also be explored.

子宫内膜干细胞/祖细胞是干细胞的一种,具有自我更新和分化成多种细胞类型的能力。它们存在于子宫内膜中,与邻近细胞和细胞外基质形成壁龛。子宫内膜干细胞/祖细胞与壁龛之间的相互作用在维持、修复和再生子宫内膜结构和功能方面发挥着重要作用。本综述将讨论子宫内膜干/祖细胞及其壁龛的特点和功能、它们之间的相互作用机制,以及它们在子宫内膜再生和疾病中的作用。最后,还将探讨其应用前景。
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引用次数: 0
Murine and Human-Purified very Small Embryonic-like Stem Cells (VSELs) Express Purinergic Receptors and Migrate to Extracellular ATP Gradient 小鼠和人类纯化的极小胚胎样干细胞 (VSEL) 表达嘌呤能受体并向细胞外 ATP 梯度迁移
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-18 DOI: 10.1007/s12015-024-10716-4
Kamila Bujko, Katarzyna Brzezniakiewicz-Janus, Justyna Jarczak, Magdalena Kucia, Mariusz Z. Ratajczak

Purinergic signaling is an ancient primordial signaling system regulating tissue development and specification of various types of stem cells. Thus, functional purinergic receptors are present in several types of cells in the body, including multiple populations of stem cells. However, one stem cell type that has not been evaluated for expression of purinergic receptors is very small embryonic stem cells (VSELs) isolated from postnatal tissues. Herein, we report that human umbilical cord blood (UCB) and murine bone marrow (BM) purified VSELs express mRNA for P1 and P2 purinergic receptors and CD39 and CD73 ectonucleotidases converting extracellular ATP (eATP) into its signaling metabolite extracellular adenosine (eAdo), that antagonizes eATP effects. More importantly, we demonstrate that human and murine VSELs respond by chemotaxis to eATP, and eAdo inhibits this migration. These responses to eATP are mediated by activation of Nlrp3 inflammasome, and exposure of VSELs to its specific inhibitor MCC950 abolished the chemotactic response to ATP. We conclude that purinergic signaling plays an essential, underappreciated role in the biology of these cells and their potential role in response to tissue/organ injuries.

Graphical Abstract

嘌呤能信号是一种古老的原始信号系统,它调节组织发育和各类干细胞的规格。因此,功能性嘌呤能受体存在于体内多种类型的细胞中,包括多种干细胞群。然而,从出生后组织中分离出的极小胚胎干细胞(VSELs)是一种尚未进行嘌呤能受体表达评估的干细胞类型。在此,我们报告了人脐带血(UCB)和小鼠骨髓(BM)纯化的VSELs表达P1和P2嘌呤能受体的mRNA以及CD39和CD73外切核苷酸酶,它们能将细胞外ATP(eATP)转化为其信号代谢产物细胞外腺苷(eAdo),从而拮抗eATP的作用。更重要的是,我们证明了人类和鼠类 VSEL 对 eATP 的趋化反应,而 eAdo 可抑制这种迁移。这些对eATP的反应是由Nlrp3炎性体的激活介导的,而将VSEL暴露于其特异性抑制剂MCC950中会取消对ATP的趋化反应。我们的结论是,嘌呤能信号在这些细胞的生物学及其对组织/器官损伤的潜在反应中发挥着重要的、未被充分认识的作用。
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引用次数: 0
Prominent Expression of COL2A1, ACAN and IHH Genes are Observed in the Differentiation of Human Hematopoietic Stem Cells into Articular Type of Chondrocytes 在人类造血干细胞向关节型软骨细胞分化过程中观察到 COL2A1、ACAN 和 IHH 基因的显著表达
IF 4.8 3区 医学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-04-18 DOI: 10.1007/s12015-023-10665-4
Echambadi Loganathan Samundeshwari, Surekha kattaru, Sireesha Kodavala, Chodimella Chandrasekhar, Potukuchi Venkata Gurunadha Krishna Sarma
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引用次数: 0
期刊
Stem Cell Reviews and Reports
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