Protective effects of conditioned media of immortalized stem cells from human exfoliated deciduous teeth on pressure ulcer formation.

Protective effects of conditioned media of immortalized stem cells from human exfoliated deciduous teeth on pressure ulcer formation.
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DOI:
10.3389/fimmu.2022.1010700
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发表时间:
2022
影响因子:
7.3
通讯作者:
Yoshimoto, Takayuki
Yoshimoto, Takayuki
中科院分区:
医学2区
文献类型:
--
作者:
Katahira, Yasuhiro;Murakami, Fumihiro;Inoue, Shinya;Miyakawa, Satomi;Sakamoto, Eri;Furusaka, Yuma;Watanabe, Aruma;Sekine, Ami;Kuroda, Masahiko;Hasegawa, Hideaki;Mizoguchi, Izuru;Yoshimoto, Takayuki

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压力性溃疡(PU)在全球范围内随着年龄的增长而增加,但没有有效的病因治疗。虽然间充质干细胞(MSC)促进皮肤伤口愈合,MSC的条件培养基(CM)对缺血再灌注损伤诱导的皮肤PU形成的影响研究甚少。为了解决这个问题,本文中,我们首先从人脱落乳牙(SHED)建立了永生化干细胞系。该细胞系显示出具有上级特征,因为其无限且旺盛地生长,并且稳定且一致地分泌多种细胞因子。使用从永生化SHED细胞系获得的CM,我们研究了使用两个磁性板对皮肤缺血再灌注小鼠模型PU形成的治疗潜力。这是第一项研究表明,从永生化SHED CM发挥PU形成的治疗作用,通过促进血管生成和氧化应激抗性,通过血管内皮生长因子和肝细胞生长因子。因此,MSC的CM具有有效的治疗效果,而这些疗法尚未在人类医学中实施。为了尽可能地满足生产和质量控制的法规要求,有必要生产始终安全有效的CM。干细胞的永生化可能是满足监管要求的突破之一,从而为创造一种新型的无细胞再生医学开辟了一条新的途径,尽管需要进一步研究质量控制。
Pressure ulcers (PUs) are increasing with aging worldwide, but there is no effective causal therapy. Although mesenchymal stem cells (MSCs) promote cutaneous wound healing, the effects of the conditioned medium (CM) of MSCs on cutaneous PU formation induced by ischemia-reperfusion injury have been poorly investigated. To address this issue, herein, we first established an immortalized stem cell line from human exfoliated deciduous teeth (SHED). This cell line was revealed to have superior characteristics in that it grows infinitely and vigorously, and stably and consistently secretes a variety of cytokines. Using the CM obtained from the immortalized SHED cell line, we investigated the therapeutic potential on a cutaneous ischemia-reperfusion mouse model for PU formation using two magnetic plates. This is the first study to show that CM from immortalized SHEDs exerts therapeutic effects on PU formation by promoting angiogenesis and oxidative stress resistance through vascular endothelial growth factor and hepatocyte growth factor. Thus, the CM of MSCs has potent therapeutic effects, whereas these therapies have not been implemented in human medicine. To try to meet the regulatory requirements for manufacturing and quality control as much as possible, it is necessary to produce CM that is consistently safe and effective. The immortalization of stem cells could be one of the breakthroughs to meet the regulatory requirements and consequently open up a novel avenue to create a novel type of cell-free regenerative medicine, although further investigation into the quality control is warranted.
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