Mattiucci Domenico, Maurizi Giulia, Izzi Valerio, Cenci Lorenzo, Ciarlantini Marco, Mancini Stefania, Mensà Emanuela, Pascarella Raffaele, Vivarelli Marco, Olivieri Attilio, Leoni Pietro, Poloni Antonella
Dipartimento Scienze Cliniche e Molecolari, Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy.
Faculty of Biochemistry and Molecular Medicine, Center for Cell-Matrix Research and Biocenter Oulu, University of Oulu, Oulu, Finland.
J Cell Physiol. 2018 Feb;233(2):1500-1511. doi: 10.1002/jcp.26037. Epub 2017 Aug 3.
In bone marrow (BM), hematopoietic elements are mingled with adipocytes (BM-A), which are the most abundant stromal component in the niche. BM-A progressively increase with aging, eventually occupying up to 50% of BM cavities. In this work, the role played by BM-A was explored by studying primary human BM-A isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human hematopoietic stem cells (HSC) by the long-term culture initiating cell (LTC-IC) assay. Findings demonstrated that BM-A are capable of supporting HSC survival in the LTC-IC assay, since after 5 weeks of co-culture, HSC were still able to proliferate and differentiate. Furthermore, critical molecules such as C-X-C motif chemokine 12 (CXCL12), interleukin (IL)-8, colony-stimulating factor 3 (CSF3), and leukaemia inhibitory factor (LIF), were expressed at similar levels in BM-A and in primary human BM mesenchymal stromal cells (BM-MSC), whereas IL-3 was higher in BM-A. Interestingly, BM-A displayed a different gene expression profile compared with subcutaneous adipose tissue adipocytes (AT-A) collected from abdominal surgery patients, especially in terms of regulation of lipid metabolism, stemness genes, and white-to-brown differentiation pathways. Accordingly, analysis of the gene pathways involved in hematopoiesis regulation showed that BM-A are more closely related to BM-MSC than to AT-A. The present data suggest that BM-A play a supporting role in the hematopoietic niche and directly sustain HSC survival.
在骨髓（BM）中，造血细胞与脂肪细胞（BM-A）混合存在，脂肪细胞是骨髓微环境中最丰富的基质成分。BM-A随年龄增长而逐渐增加，最终占据高达50%的骨髓腔。在这项研究中，通过对从髋关节手术患者分离的原代人BM-A进行分子水平的微阵列分析，以及在功能水平上通过长期培养起始细胞（LTC-IC）试验评估其与原代人造血干细胞（HSC）的关系，来探索BM-A所起的作用。研究结果表明，在LTC-IC试验中，BM-A能够支持HSC存活，因为共培养5周后，HSC仍能够增殖和分化。此外，关键分子如C-X-C基序趋化因子12（CXCL12）、白细胞介素（IL）-8、集落刺激因子3（CSF3）和白血病抑制因子（LIF），在BM-A和原代人骨髓间充质基质细胞（BM-MSC）中的表达水平相似，而IL-3在BM-A中的表达更高。有趣的是，与从腹部手术患者收集的皮下脂肪组织脂肪细胞（AT-A）相比，BM-A表现出不同的基因表达谱，特别是在脂质代谢调节、干性基因和白-棕分化途径方面。因此，对参与造血调节的基因途径分析表明，BM-A与BM-MSC的关系比与AT-A更为密切。目前的数据表明，BM-A在造血微环境中发挥支持作用，并直接维持HSC的存活。
