Woods Kevin, Guezguez Borhane
German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
Department of Hematology and Oncology, University Medical Center Mainz, Mainz, Germany.
Front Cell Dev Biol. 2021 Aug 10;9:714716. doi: 10.3389/fcell.2021.714716. eCollection 2021.
Mesenchymal stromal cells (MSCs) are a heterogenous cell population found in a wide range of tissues in the body, known for their nutrient-producing and immunomodulatory functions. In the bone marrow (BM), these MSCs are critical for the regulation of hematopoietic stem cells (HSC) that are responsible for daily blood production and functional immunity throughout an entire organism's lifespan. Alongside other stromal cells, MSCs form a specialized microenvironment BM tissue called "niche" that tightly controls HSC self-renewal and differentiation. In addition, MSCs are crucial players in maintaining bone integrity and supply of hormonal nutrients due to their capacity to differentiate into osteoblasts and adipocytes which also contribute to cellular composition of the BM niche. However, MSCs are known to encompass a large heterogenous cell population that remains elusive and poorly defined. In this review, we focus on deciphering the BM-MSC biology through recent advances in single-cell identification of hierarchical subsets with distinct functionalities and transcriptional profiles. We also discuss the contribution of MSCs and their osteo-adipo progeny in modulating the complex direct cell-to-cell or indirect soluble factors-mediated interactions of the BM HSC niche during homeostasis, aging and myeloid malignancies. Lastly, we examine the therapeutic potential of MSCs for rejuvenation and anti-tumor remedy in clinical settings.
间充质基质细胞（MSCs）是存在于人体多种组织中的异质性细胞群体，以其营养生成和免疫调节功能而闻名。在骨髓（BM）中，这些MSCs对于调节造血干细胞（HSC）至关重要，造血干细胞负责在整个生物体的生命周期内进行日常血液生成和功能性免疫。与其他基质细胞一起，MSCs形成了一种特殊的骨髓组织微环境，称为“龛位”，它严格控制着HSC的自我更新和分化。此外，由于MSCs能够分化为成骨细胞和脂肪细胞，这也有助于骨髓龛位的细胞组成，因此它们在维持骨骼完整性和激素营养供应方面起着关键作用。然而，已知MSCs包含大量异质性细胞群体，其特性仍然难以捉摸且定义不清。在这篇综述中，我们通过在单细胞水平上对具有不同功能和转录谱的分层亚群进行鉴定的最新进展，重点解读骨髓间充质干细胞的生物学特性。我们还讨论了在稳态、衰老和髓系恶性肿瘤过程中，MSCs及其骨-脂肪前体细胞在调节骨髓造血干细胞龛位复杂的直接细胞间或间接可溶性因子介导的相互作用中的作用。最后，我们研究了MSCs在临床环境中用于恢复活力和抗肿瘤治疗的潜力。
