Oeller Michaela, Schally Tanja, Zimmermann Georg, Lauth Wanda, Schallmoser Katharina, Rohde Eva, Laner-Plamberger Sandra
Department for Transfusion Medicine, University Hospital of Salzburg (SALK), Paracelsus Medical University (PMU) Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria.
GMP Laboratory, PMU Salzburg, Strubergasse 21, 5020 Salzburg, Austria.
Int J Mol Sci. 2024 Nov 23;25(23):12589. doi: 10.3390/ijms252312589.
In regenerative medicine, stromal cells are supposed to play an important role by modulating immune responses and differentiating into various tissue types. The aim of this study was to investigate the influence of heparin, frequently used as an anticoagulant in human platelet lysate (HPL)-supplemented cell cultures, on the expression of non-coding RNA species, particularly microRNAs (miRNA), which are pivotal regulators of gene expression. Through genomic analysis and quantitative RT-PCR, we assessed the differential impact of heparin on miRNA expression in various stromal cell types, derived from human bone marrow, umbilical cord and white adipose tissue. Our results demonstrate that heparin significantly alters miRNA expression, with distinct up- and downregulation patterns depending on the original tissue source of human stromal cells. Furthermore, our analyses indicate that these heparin-induced alterations in miRNA expression profiles influence critical cellular processes, including proliferation, apoptosis and differentiation. In conclusion, our study highlights that heparin not only fulfills its primary role as an efficient anticoagulant but can also modulate important regulatory pathways in stromal cells by influencing miRNA expression. This may alter cellular properties and thus influence stromal cell-based therapeutic applications in regenerative medicine.
在再生医学中,基质细胞被认为通过调节免疫反应和分化为各种组织类型发挥重要作用。本研究的目的是探讨肝素(在补充人血小板裂解物(HPL)的细胞培养中常用作抗凝剂)对非编码RNA种类,特别是微小RNA(miRNA,基因表达的关键调节因子)表达的影响。通过基因组分析和定量逆转录聚合酶链反应,我们评估了肝素对源自人骨髓、脐带和白色脂肪组织的各种基质细胞类型中miRNA表达的不同影响。我们的结果表明,肝素显著改变miRNA表达,根据人基质细胞的原始组织来源呈现出明显的上调和下调模式。此外,我们的分析表明,这些肝素诱导的miRNA表达谱改变影响关键细胞过程,包括增殖、凋亡和分化。总之,我们的研究强调肝素不仅作为一种有效的抗凝剂发挥其主要作用,还可以通过影响miRNA表达来调节基质细胞中的重要调节途径。这可能会改变细胞特性,从而影响再生医学中基于基质细胞的治疗应用。