Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
Front Immunol. 2023 Jan 13;13:1010700. doi: 10.3389/fimmu.2022.1010700. eCollection 2022.
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.
压力性溃疡（PU）在全球范围内随着人口老龄化而增加，但目前尚无有效的因果治疗方法。间充质干细胞（MSCs）虽然可以促进皮肤伤口愈合，但 MSCs 条件培养基（CM）对缺血再灌注损伤引起的皮肤 PU 形成的影响尚未得到充分研究。为了解决这个问题，我们首先从人脱落乳牙中建立了一个永生化干细胞系（SHED）。该细胞系具有无限生长、活力旺盛、稳定一致地分泌多种细胞因子等优异特性。使用从永生化 SHED 细胞系获得的 CM，我们使用两个磁板研究了其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，通过促进血管内皮生长因子和肝细胞生长因子介导的血管生成和氧化应激抗性，来自永生化 SHED 的 CM 对 PU 形成具有治疗作用。因此，MSCs 的 CM 具有很强的治疗作用，而这些治疗方法尚未在人类医学中实施。为了尽可能满足制造和质量控制的监管要求，有必要生产出一致安全且有效的 CM。干细胞的永生化可能是满足监管要求的突破之一，从而为创造新型无细胞再生医学开辟新途径，尽管有必要进一步研究质量控制。
