Gabrielyan Anastasia, Quade Mandy, Gelinsky Michael, Rösen-Wolff Angela
Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Stem Cell Res. 2020 May;45:101814. doi: 10.1016/j.scr.2020.101814. Epub 2020 Apr 20.
Bone marrow stromal cells (BMSC) are highly attractive for tissue engineering due to their ability to differentiate into different cell types, to expand extensively in vitro and to release paracrine soluble factors with a high regenerative potential. They were observed to migrate towards the sites of injury in response to chemotactic signals in vivo. During the last years hypoxia has become a proven method to control proliferation, differentiation and multipotency of BMSC. Conditioned medium from hypoxia-treated BMSC (Hypoxia-conditioned Medium; HCM) has been shown to have various favorable properties on tissue regeneration - such as on cell recruitment, wound healing, angiogenesis and revascularization. Due to this regenerative potential many studies attempt to further characterize HCM and its main functional components. In this study we used HCM generated from umbilical cord mesenchymal stem cells (UC-MSC) instead of BMSC, because GMP-verified methods were used to isolate and cultivate the cells and ensure their constant quality. UC-MSC have a high regenerative potential and are still immunologically naive and therefore highly unlikely to cause an immune reaction. In our article we took the first steps to closer investigate the role of umbilical cord MSC-derived HCM components, namely stromal cell-derived factor 1 (SDF-1α), interleukin 11 (IL-11) and soluble vascular cell adhesion molecule 1 (sVCAM-1).
Our results show previously unknown roles of IL-11 and sVCAM-1 in the attraction of BMSC. The synergistic effect of the investigated protein mixture consisting of IL-11, sVCAM-1 and SDF-1α as well as those recombinant proteins alone revealed a significantly higher chemoattractive capacity towards human BMSC compared to normoxic control medium. Both, the protein mixtures and proteins alone as well as UC-HCM showed an angiogenic effect by promoting the formation of significantly longer tubule structures and higher amounts of junctions and tubules compared to normoxic control medium.
By showing the prominent upregulation of IL-11, sVCAM-1 and SDF-1α under hypoxic conditions compared to normoxic control and revealing their crucial role in migration of human BMSC we took a further step forward in characterization of the chemoattractive components of HCM.
骨髓基质细胞（BMSC）因其具有分化为不同细胞类型、在体外大量扩增以及释放具有高再生潜能的旁分泌可溶性因子的能力，在组织工程领域极具吸引力。在体内，人们观察到它们会响应趋化信号向损伤部位迁移。在过去几年中，缺氧已成为一种控制BMSC增殖、分化和多能性的成熟方法。缺氧处理的BMSC的条件培养基（缺氧条件培养基；HCM）已被证明在组织再生方面具有多种有利特性，如在细胞募集、伤口愈合、血管生成和血管重建方面。由于这种再生潜能，许多研究试图进一步表征HCM及其主要功能成分。在本研究中，我们使用了由脐带间充质干细胞（UC-MSC）而非BMSC产生的HCM，因为采用了经过GMP验证的方法来分离和培养细胞，并确保其质量稳定。UC-MSC具有高再生潜能，且仍处于免疫幼稚状态，因此极不可能引发免疫反应。在我们的文章中，我们迈出了第一步，更深入地研究脐带间充质干细胞来源的HCM成分，即基质细胞衍生因子1（SDF-1α）、白细胞介素11（IL-11）和可溶性血管细胞黏附分子1（sVCAM-1）的作用。
我们的结果显示了IL-11和sVCAM-1在吸引BMSC方面此前未知的作用。由IL-11、sVCAM-1和SDF-1α组成的研究蛋白混合物以及单独的那些重组蛋白的协同作用，与常氧对照培养基相比，对人BMSC显示出显著更高的趋化能力。与常氧对照培养基相比，蛋白混合物、单独的蛋白以及UC-HCM均通过促进形成明显更长的管状结构以及更多的连接点和小管而显示出血管生成作用。
通过显示与常氧对照相比，缺氧条件下IL-11、sVCAM-1和SDF-1α显著上调，并揭示它们在人BMSC迁移中的关键作用，我们在表征HCM趋化成分方面又向前迈进了一步。
