Avila-Portillo Luz M, Aristizabal Fabio, Riveros Angela, Abba Martin C, Correa Diego
Departamento de Farmacia, Universidad Nacional de Colombia, Bogotá, Colombia.
Stem Medicina Regenerativa/CryoHoldco, Bogotá, Colombia.
Stem Cells Int. 2020 Feb 15;2020:5045124. doi: 10.1155/2020/5045124. eCollection 2020.
Mesenchymal stem/stromal cells (MSCs) exhibit multidifferentiation potential, paralleled with immunomodulatory and trophic properties that make them viable alternative tools for the treatment of degenerative disorders, allograft rejection, autoimmune diseases, and tissue regeneration. MSC functional attributes can be modulated by exposing them to inflammatory-stimulating microenvironments (, priming) before their therapeutic use. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that plays key roles in immune response and hematopoiesis modulation through direct effects on hematopoietic progenitors' proliferation, survival, and mobilization. Despite the established roles of MSCs supporting hematopoiesis, the effects of G-CSF on MSCs biology have not been thoroughly explored. This study reveals that G-CSF has also direct effects on adipose-derived MSCs (ADSCs), modulating their functions. Herein, microarray-based transcriptomic analysis shows that G-CSF stimulation results in modulation of various signaling pathways including ones related with the metabolism of hyaluronan (HA), conferring a profile of cell mobilization to ADSCs, mediated in a cell-intrinsic fashion in part by reducing CD44 expression and HA synthesis-related genes. Collectively, these data suggest a direct modulatory effect of G-CSF on ADSC function, potentially altering their therapeutic capacity and thus the design of future clinical protocols.
间充质干/基质细胞（MSCs）具有多向分化潜能，同时具备免疫调节和营养特性，这使得它们成为治疗退行性疾病、同种异体移植排斥反应、自身免疫性疾病和组织再生的可行替代工具。在治疗应用前，将MSCs暴露于炎症刺激微环境（即预处理）可调节其功能属性。粒细胞集落刺激因子（G-CSF）是一种细胞因子，通过对造血祖细胞的增殖、存活和动员产生直接影响，在免疫反应和造血调节中发挥关键作用。尽管MSCs在支持造血方面的作用已得到确立，但G-CSF对MSCs生物学特性的影响尚未得到充分研究。本研究表明，G-CSF对脂肪来源的间充质干细胞（ADSCs）也有直接影响，可调节其功能。在此，基于微阵列的转录组分析表明，G-CSF刺激导致多种信号通路的调节，包括与透明质酸（HA）代谢相关的信号通路，赋予ADSCs细胞动员特性，部分是通过细胞内在方式介导的，即降低CD44表达和HA合成相关基因。总体而言，这些数据表明G-CSF对ADSC功能具有直接调节作用，可能改变其治疗能力，从而影响未来临床方案的设计。
