Department of Cardiac Surgery, University Hospital Basel, 4031 Basel, Switzerland.
Department of Biomedicine, University Basel, 4031 Basel, Switzerland.
Int J Mol Sci. 2021 Jul 24;22(15):7920. doi: 10.3390/ijms22157920.
The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor ( < 0.001) and the number of proliferating cells ( < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.
间充质基质/干细胞（MSC）治疗心肌缺血的治疗潜力强烈依赖于其旁分泌介导的作用及其在梗死心肌等恶劣环境中的植入能力。脂肪组织来源的基质血管部分（SVF）细胞是一种混合群体，主要由 MSC 和血管细胞组成，以其高血管生成潜力而闻名。先前的研究表明，SVF 细胞在灌注生物反应器培养后的体外组织（补片）中组织化后，其血管生成潜力进一步增加。本研究旨在研究在恶劣缺氧条件下体外培养对 SVF 细胞的细胞成分、体内血管生成潜力和植入能力的可能变化。这模拟了补片在低灌注心肌中植入后可能出现的血管化延迟。为此，将人 SVF 细胞接种到胶原海绵上，在灌注生物反应器中于常氧或缺氧（分别为 21%和<1%的氧张力）下培养 5 天，并在裸鼠中皮下植入 3 天和 28 天。与环境条件培养相比，低氧张力不会改变体外 SVF 成分，显示出相似数量的 MSC 以及内皮细胞和壁细胞。然而，体外低氧培养显著增加了血管内皮生长因子的释放（<0.001）和增殖细胞的数量（<0.00001）。此外，与常氧培养相比，在植入 28 天后，缺氧暴露显著增加了工程组织中的血管长度密度。与常氧培养相比，在体内 3 天和 28 天后，缺氧培养构建体中的人细胞和人增殖细胞的数量也显著增加。这些发现表明，可能的体内氧供应延迟不会损害 SVF 补片的血管化潜力，这使其有资格在心肌缺血模型中进行评估。
