Heart Center of the University of Cologne, Department of Cardiothoracic Surgery, Cologne, Germany.
Cytotherapy. 2012 Jul;14(6):670-8. doi: 10.3109/14653249.2012.663483. Epub 2012 Mar 12.
In the past, cell transplantation strategies for the treatment of heart failure have shown promising results in experimental and clinical studies. Bone marrow (BM)-derived stem cells represent the most frequently used cell population. Within this heterogeneous cell population, mesenchymal stromal cells (MSC) have been identified to induce therapeutic effects, mainly through paracrine mechanisms. Because of their low frequency in native tissues, in vitro cell culture expansion is mandatory prior to transplantation. We sought to identify patient-specific cardiovascular risk factors influencing the proliferative potential of MSC.
BM aspirates from 51 patients undergoing elective cardiac surgery were analyzed for MSC frequency and cell culture expansion potential. Fibroblastic colony-forming units (CFU-F) were quantified for culture conditions applying autologous (AS) or fetal bovine serum (FBS) and different basic media. Univariate and multivariate analyzes were performed in order to determine the impact of patient-specific factors on CFU-F numbers.
Expanded MSC showed a specific immune phenotype and displayed adipogenic, chondrogeneic and osteogeneic differentiation potential. CFU-F numbers did not differ under AS or FBS supplementation. Elevated numbers of mononuclear cells, diabetes mellitus, steroid treatment, chronic obstructive pulmonary disease, renal failure, high euroSCORE and impaired left ventricular function were significant determinants for higher CFU-F numbers.
The impact of specific cardiovascular risk factors on MSC fitness could be determined. These results may help to establish patient profiling in order to identify patients suitable for autologous MSC transplantation, and might lead to the identification of disease-related mechanisms of stem cell activation.
过去，细胞移植策略治疗心力衰竭在实验和临床研究中显示出了有希望的结果。骨髓（BM）来源的干细胞是最常使用的细胞群体。在这个异质细胞群体中，间充质基质细胞（MSC）已被确定通过旁分泌机制诱导治疗效果。由于它们在天然组织中的频率较低，在移植前必须进行体外细胞培养扩增。我们试图确定影响 MSC 增殖潜能的患者特异性心血管危险因素。
分析了 51 例行择期心脏手术的患者的 BM 抽吸物，以分析 MSC 的频率和细胞培养扩增潜力。为了确定患者特异性因素对 CFU-F 数量的影响，对应用自体（AS）或胎牛血清（FBS）和不同基本培养基的培养条件进行了单变量和多变量分析。
扩增的 MSC 表现出特定的免疫表型，并显示出成脂、成软骨和成骨分化潜能。在 AS 或 FBS 补充下，CFU-F 数量没有差异。单核细胞数量增加、糖尿病、类固醇治疗、慢性阻塞性肺疾病、肾衰竭、高 euroSCORE 和左心室功能受损是 CFU-F 数量增加的显著决定因素。
可以确定特定心血管危险因素对 MSC 适应性的影响。这些结果可能有助于建立患者概况，以确定适合自体 MSC 移植的患者，并可能导致识别与疾病相关的干细胞激活机制。
