Department of Cardiology, Gifu Municipal Hospital, Gifu, Japan.
Department of Dermatology, Sapporo City General Hospital, Sapporo, Japan.
Stem Cells Transl Med. 2024 Jun 14;13(6):532-545. doi: 10.1093/stcltm/szae018.
The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.
干细胞治疗的优势在于通过协同的多效作用来再生组织。在许多干细胞类型中，间充质干细胞（MSCs）由于具有多效性旁观者效应而被广泛用于临床应用，其由异质性群体组成。Muse 细胞是多能样/巨噬样干细胞，分布在骨髓、外周血和器官结缔组织中，其特征是多能表面标志物阶段特异性胚胎抗原-3 阳性。Muse 细胞占 MSCs 的~1%到几个百分点。虽然 Muse 细胞和 MSCs 具有一些共同的特征，如间充质表面标志物表达和旁观者效应，但 Muse 细胞表现出 MSCs 中没有观察到的独特特征。Muse 细胞的这些独特特征包括静脉注射后选择性归巢到受损组织，而不像 MSCs 那样被滞留在肺部，通过吞噬作用分化替代广泛的受损/凋亡细胞，以及供体细胞使用的长期免疫耐受性。在这篇综述中，我们重点介绍了通过静脉注射供体 Muse 细胞进行的临床前研究和临床试验中阐明的 Muse 细胞的基本特性，这些研究无需 HLA 匹配测试或免疫抑制治疗。MSCs 被认为可分化为成骨细胞、软骨细胞和成脂细胞，而其分化范围一直存在争议。Muse 细胞可能为观察到的 MSC 广泛分化潜能提供线索，尽管这种潜能出现的频率较低。此外，Muse 细胞的利用可能为临床治疗提供一种新策略。
