Muratoğlu Bihter, Özdemir Cansu, Eylem Cemil Can, Reçber Tuba, Nemutlu Emirhan, Alpdündar-Bulut Esin, Vargel İbrahim, Uçkan-Çetinkaya Duygu
Institute of Health Sciences, Department of Stem Cell Sciences and Center for Stem Cell Research and Development (PEDI-STEM), Hacettepe University, Ankara, Türkiye; Institute of Health Sciences, Department of Stem Cell Sciences, Hacettepe University, Ankara, Türkiye.
Institute of Health Sciences, Department of Stem Cell Sciences and Center for Stem Cell Research and Development (PEDI-STEM), Hacettepe University, Ankara, Türkiye; Institute of Health Sciences, Department of Stem Cell Sciences, Hacettepe University, Ankara, Türkiye.
Bone. 2025 Apr;193:117413. doi: 10.1016/j.bone.2025.117413. Epub 2025 Feb 1.
Bone marrow is a complex tissue featuring distinct cellular organization and diverse cell types. Bone marrow adipose tissue (BMAT) is a dynamic component crucial for tissue function and disease processes. This study explores differences between bone marrow-derived mesenchymal stem cells (BM-MSCs) and BMAT-derived mesenchymal stem cells (BMAT-MSCs), isolated from the same cavity, examining their differentiation potential and secretory profiles. BM-MSCs and BMAT-MSCs both exhibit classical mesenchymal characteristics, with over 90 % positivity for markers such as CD105 and CD29. Notably, BMAT-MSCs display significantly higher differentiation potential than BM-MSCs, with enhanced osteogenic and adipogenic capabilities, as indicated by increased calcium accumulation and lipid storage. In Fanconi anemia (FA) and acute myeloid leukemia (AML), osteogenic potential is limited, indicating impaired differentiation under these pathological conditions. Gene expression analysis of adipogenic molecules and metabolic regulators revealed significant differences in expression profile between BM- and BMAT-MSCs, particularly during adipogenic differentiation, indicating distinct characteristics that were more notable in FAs and AMLs. Furthermore, metabolomic profiling of BM plasma, using GC-MS for in-vivo niche reflection, and lipid analysis via LC-qTOF-MS show significant lipidomic alterations in patient samples, highlighting metabolic dysregulation and lipid remodeling. Lipid-mediated signaling and membrane composition changes appear integral to disease mechanisms. In conclusion, this study highlights the distinctive molecular and metabolomic profiles and adaptive mechanisms of BM- and BMAT-MSCs in bone marrow pathologies.
骨髓是一种复杂组织，具有独特的细胞结构和多种细胞类型。骨髓脂肪组织（BMAT）是组织功能和疾病进程中至关重要的动态组成部分。本研究探究了从同一腔隙分离出的骨髓间充质干细胞（BM-MSCs）和BMAT间充质干细胞（BMAT-MSCs）之间的差异，检测了它们的分化潜能和分泌谱。BM-MSCs和BMAT-MSCs均表现出典型的间充质特征，CD105和CD29等标志物的阳性率超过90%。值得注意的是，BMAT-MSCs的分化潜能显著高于BM-MSCs，其成骨和成脂能力增强，表现为钙积累和脂质储存增加。在范可尼贫血（FA）和急性髓系白血病（AML）中，成骨潜能受限，表明在这些病理条件下分化受损。对成脂分子和代谢调节因子的基因表达分析显示，BM-MSCs和BMAT-MSCs之间的表达谱存在显著差异，尤其是在成脂分化过程中，这表明在FA和AML中更显著的不同特征。此外，使用气相色谱-质谱联用（GC-MS）对BM血浆进行代谢组学分析以反映体内微环境，以及通过液相色谱-四极杆飞行时间质谱（LC-qTOF-MS）进行脂质分析，结果显示患者样本中存在显著的脂质组改变，突出了代谢失调和脂质重塑。脂质介导的信号传导和膜组成变化似乎是疾病机制的重要组成部分。总之，本研究突出了BM-MSCs和BMAT-MSCs在骨髓病变中的独特分子和代谢组学特征及适应性机制。
