McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA 19104,
Eur Cell Mater. 2017 Oct 27;34:217-231. doi: 10.22203/eCM.v034a14.
Mesenchymal stem cells (MSCs) display substantial cell-to-cell variation. This heterogeneity manifests among donors, among tissue sources, and within cell populations. Such pervasive variability complicates the use of MSCs in regenerative applications and may limit their therapeutic efficacy. Most conventional assays measure MSC properties in bulk and, as a consequence, mask this cell-to-cell variation. Recent studies have identified extensive variability amongst and within clonal MSC populations, in dimensions including functional differentiation capacity, molecular state (e.g. epigenetic, transcriptomic, and proteomic status), and biophysical properties. While the origins of these variations remain to be elucidated, potential mechanisms include in vivo micro-anatomical heterogeneity, epigenetic bistability, and transcriptional fluctuations. Emerging tools for single cell analysis of MSC gene and protein expression may yield further insight into the mechanisms and implications of single cell variation amongst these cells, and ultimately improve the clinical utility of MSCs in tissue engineering and regenerative medicine applications. This review outlines the dimensions across which MSC heterogeneity is present, defines some of the known mechanisms that govern this heterogeneity, and highlights emerging technologies that may further refine our understanding and improve our clinical application of this unique cell type.
间充质干细胞（MSCs）表现出显著的细胞间变异性。这种异质性表现在供体之间、组织来源之间和细胞群体内。这种普遍存在的可变性使得 MSCs 在再生应用中的使用变得复杂，并可能限制其治疗效果。大多数传统的检测方法在整体上测量 MSC 的特性，因此掩盖了这种细胞间的变异性。最近的研究已经在功能分化能力、分子状态（如表观遗传、转录组和蛋白质组状态）和生物物理特性等方面确定了克隆 MSC 群体之间和内部的广泛变异性。虽然这些变异的起源仍有待阐明，但潜在的机制包括体内微解剖异质性、表观遗传双稳定性和转录波动。用于 MSC 基因和蛋白质表达单细胞分析的新兴工具可能会进一步深入了解这些细胞中单细胞变异的机制和意义，并最终提高 MSCs 在组织工程和再生医学应用中的临床实用性。本综述概述了 MSC 异质性存在的维度，定义了一些控制这种异质性的已知机制，并强调了可能进一步完善我们对这种独特细胞类型的理解和改善我们临床应用的新兴技术。
