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电离辐射剂量率的变化会影响脂肪来源干细胞的细胞周期进程。

Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells.

机构信息

Bioengineering Department, Clemson University, Clemson, South Carolina, United States of America.

Physics and Astronomy Department, Clemson University, Clemson, South Carolina, United States of America.

出版信息

PLoS One. 2021 Apr 27;16(4):e0250160. doi: 10.1371/journal.pone.0250160. eCollection 2021.

DOI:10.1371/journal.pone.0250160
PMID:33905436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8078807/
Abstract

Biomedical use of radiation is utilized in effective diagnostic and treatment tools, yet can introduce risks to healthy tissues. High energy photons used for diagnostic purposes have high penetration depth and can discriminate multiple tissues based on attenuation properties of different materials. Likewise, the ability to deposit energy at various targets within tumors make the use of photons effective treatment for cancer. Radiation focused on a tumor will deposit energy when it interacts with a biological structure (e.g. DNA), which will result in cell kill should repair capacity of the tissue be overwhelmed. Likewise, damage to normal, non-cancerous tissues is a consequence of radiation that can lead to acute or late, chronic toxicity profiles. Adipose derived stem cells (ADSCs) are mesenchymal stem cells that have been proven to have similar characteristics to bone marrow derived stem cells, except that they are much easier to obtain. Within the body, ADSCs act as immunomodulators and assist with the maintenance and repair of tissues. They have been shown to have excellent differentiation capability, making them an extremely viable option for stem cell therapies and regenerative medicine applications. Due to the tissue ADSCs are derived from, they are highly likely to be affected by radiation therapy, especially when treating tumors localized to structures with relatively high ADSC content (eg., breast cancer). For this reason, the purpose behind this research is to better understand how ADSCs are affected by doses of radiation comparable to a single fraction of radiation therapy. We also measured the response of ADSCs to exposure at different dose rates to determine if there is a significant difference in the response of ADSCs to radiation therapy relevant doses of ionizing radiation. Our findings indicate that ADSCs exposed to Cesium (Cs 137)-gamma rays at a moderate dose of 2Gy and either a low dose rate (1.40Gy/min) or a high dose rate (7.31Gy/min) slow proliferation rate, and with cell cycle arrest in some populations. These responses ADSCs were not as marked as previously measured in other stem cell types. In addition, our results indicate that differences in dose rate in the Gy/min range typically utilized in small animal or cell irradiation platforms have a minimal effect on the function of ADSCs. The potential ADSCs have in the space of regenerative medicine makes them an ideal candidate for study with ionizing radiation, as they are one of the main cell types to promote tissue healing.

摘要

生物医学中使用的辐射被用于有效的诊断和治疗工具,但也会给健康组织带来风险。用于诊断目的的高能光子具有高穿透深度,并且可以根据不同材料的衰减特性来区分多种组织。同样,能够在肿瘤内的各种靶标沉积能量使得光子成为治疗癌症的有效手段。当辐射与生物结构(例如 DNA)相互作用时,聚焦在肿瘤上的辐射会沉积能量,如果组织的修复能力被超过,将会导致细胞死亡。同样,对正常的、非癌性组织的损伤是辐射的后果,可能导致急性或迟发性、慢性毒性谱。脂肪来源的干细胞(ADSCs)是间充质干细胞,已被证明具有与骨髓来源的干细胞相似的特征,除了它们更容易获得。在体内,ADSCs 作为免疫调节剂,有助于组织的维持和修复。它们已经显示出出色的分化能力,使它们成为干细胞治疗和再生医学应用的极有前途的选择。由于 ADSCs 来源于组织,它们很可能受到放射治疗的影响,特别是在治疗局部含有相对较高 ADSC 含量的肿瘤(例如乳腺癌)时。出于这个原因,这项研究的目的是更好地了解 ADSCs 如何受到类似于单次放射治疗剂量的辐射剂量的影响。我们还测量了 ADSCs 对不同剂量率暴露的反应,以确定 ADSCs 对与放射治疗相关的电离辐射剂量的反应是否存在显著差异。我们的研究结果表明,ADSCs 暴露于铯(Cs 137)-γ射线的中等剂量 2Gy 下,无论是低剂量率(1.40Gy/min)还是高剂量率(7.31Gy/min),其增殖速度都会减慢,并且在某些群体中细胞周期停滞。这些 ADSCs 的反应不如以前在其他干细胞类型中测量到的那样明显。此外,我们的结果表明,在小动物或细胞辐照平台中通常使用的 Gy/min 范围内的剂量率差异对 ADSCs 的功能几乎没有影响。ADSCs 在再生医学领域的潜力使它们成为研究电离辐射的理想候选物,因为它们是促进组织愈合的主要细胞类型之一。

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