Miłek Oliwia, Schwarz Katharina, Miletić Alma, Reisinger Johanna, Kovar Alexander, Behm Christian, Andrukhov Oleh
Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Front Cell Dev Biol. 2025 Mar 7;13:1532898. doi: 10.3389/fcell.2025.1532898. eCollection 2025.
Mesenchymal stromal cells (MSCs) with high expression of CD146 have superior properties for tissue regeneration. However, high variability in the rate of CD146+ cells among donors is observed. In this study, the possible reasons behind this variability in human periodontal ligament MSCs (hPDL-MSCs) were explored.
hPDL-MSCs were isolated from 22 different donors, and rates of CD146+ cells were analyzed by flow cytometry. Furthermore, populations with various rates of CD146+ cells were isolated with magnetic separation. The dependency of cell proliferation, viability, cell cycle, and osteogenic differentiation on the rates of CD146+ cells was investigated. Besides, the effects of various factors, like cell density, confluence, and inflammatory environment on the CD146+ rate and expression were analyzed.
The rate of CD146+ cells exhibited high variability between donors, with the percentage of CD146+ cells ranging from 3% to 67%. Higher percentage of CD146+ cells was associated with higher proliferation, presumably due to the higher percentage of cells in the S-phase, and higher osteogenic differentiation potential. Prolonged cell confluence and higher cell seeding density led to the decline in the rate of CD146+ cells. The surface rate of CD146 in hPDL-MSCs was stimulated by the treatment with interleukin-1β and tumor necrosis factor-α, and inhibited by the treatment with interferon-γ.
These results suggest that hPDL-MSCs with high rate of CD146+ cells are a promising subpopulation for enhancing the effectiveness of MSC-based regenerative therapies, however the rate of CD146 is affected by various factors, which must be considered for cell propagation and their potential application .
高表达CD146的间充质基质细胞(MSC)在组织再生方面具有卓越特性。然而,在供体中观察到CD146 +细胞比例存在高度变异性。本研究探讨了人牙周膜间充质干细胞(hPDL - MSC)中这种变异性背后的可能原因。
从22位不同供体中分离出hPDL - MSC,并通过流式细胞术分析CD146 +细胞比例。此外,利用磁珠分选法分离出不同CD146 +细胞比例的细胞群体。研究了细胞增殖、活力、细胞周期和成骨分化对CD146 +细胞比例的依赖性。此外,还分析了诸如细胞密度、汇合度和炎症环境等各种因素对CD146 +比例和表达的影响。
供体之间CD146 +细胞比例表现出高度变异性,CD146 +细胞百分比范围为3%至67%。较高比例的CD146 +细胞与较高的增殖相关,这可能是由于处于S期的细胞百分比更高,且具有更高的成骨分化潜力。延长细胞汇合时间和提高细胞接种密度会导致CD146 +细胞比例下降。用白细胞介素 - 1β和肿瘤坏死因子 - α处理可刺激hPDL - MSC表面CD146比例,而用干扰素 - γ处理则会抑制该比例。
这些结果表明,高比例CD146 +细胞的hPDL - MSC是提高基于MSC的再生疗法有效性的一个有前景的亚群,然而CD146比例受多种因素影响,在细胞扩增及其潜在应用中必须予以考虑。