The Effects of Plasma Exosomes of Young Individuals Compared to Old Ones on Age-Related Inflammation and Lineage Differentiation of CD34+ Umbilical Cord Blood Hematopoietic Stem Cells.

IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL
Maryam Helali, Saeid Kaviani, Shaban Alizadeh, Reza Afrisham, Mohammad Ahmadvand
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引用次数: 0

Abstract

Introduction: Cellular aging is a complicated event known for gradually reducing homeostasis, leading to a higher susceptibility to diseases and mortality. Since the behavior of Hematopoietic Stem Cells (HSCs) is potentially affected by plasma-derived exosomes, this study aimed to investigate whether the plasma-derived exosome of young and elderly human donors can deliver "youth" or "aging" signals into human umbilical cord blood-derived HSCs in vitro.

Methods: Exosomes were isolated from four young (Y-exo) and four old (O-exo) donors. Umbilical cord blood-derived HSCs were exposed to two concentrations of exosomes (5 and 10 μg/mL). Then, lineage differentiation (CD41 and CD38), the mRNA and protein expression of IL-1β and IL- 6, and NFκB activity were evaluated using flow cytometry, qRT-PCR Enzyme-Linked Immunosorbent Assay (ELISA) methods, and western blot techniques, respectively.

Results: The lineage-specific markers CD41 and CD38 expression were increased after exposure to O-exo compared to Y-exo at the concentration of 10 μg/mL (P<0.001). The HSCs treated with 10 μg/mL O-exo increased protein and mRNA expression of IL-1β and IL-6 compared to Y-exo at 10 μg/mL concentration (P<0.01). Furthermore, a significant difference was seen in p-NF-κB levels between O-exo and Y-exo at the concentration of 10 μg/mL (P=0.0014).

Conclusion: Our findings advocated the concept that circulating exosomes of old and young individuals may differently affect the pathways involved in the aging process in HSCs.Therefore, exosomes may be applied as therapeutic agents for regenerative medicine.

与老年人相比,年轻人血浆外泌体对年龄相关炎症和CD34+脐血造血干细胞谱系分化的影响
细胞衰老是一个复杂的事件,以逐渐减少体内平衡而闻名,导致更高的疾病易感性和死亡率。由于造血干细胞(hsc)的行为可能受到血浆源性外泌体的影响,本研究旨在探讨年轻和老年人类供体的血浆源性外泌体是否可以在体外向人脐带血源性hsc传递“年轻”或“衰老”信号。方法:从4例年轻供体(Y-exo)和4例老年供体(O-exo)中分离外泌体。脐带血来源的造血干细胞暴露于两种浓度的外泌体(5和10 μg/mL)。然后分别采用流式细胞术、qRT-PCR酶联免疫吸附试验(ELISA)和western blot技术检测各组细胞的谱系分化(CD41和CD38)、IL-1β和IL- 6 mRNA和蛋白表达以及NFκB活性。结果:与Y-exo浓度相比,10 μg/mL的O-exo暴露后,谱系特异性标志物CD41和CD38的表达增加(p)。结论:我们的研究结果表明,老年人和年轻人的循环外泌体可能不同地影响hsc衰老过程的途径。因此,外泌体可作为再生医学的治疗剂。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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