Department of Radiology and Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, California, USA.
PLoS One. 2009 Dec 31;4(12):e8443. doi: 10.1371/journal.pone.0008443.
Differentiation of human embryonic stem cells into endothelial cells (hESC-ECs) has the potential to provide an unlimited source of cells for novel transplantation therapies of ischemic diseases by supporting angiogenesis and vasculogenesis. However, the endothelial differentiation efficiency of the conventional embryoid body (EB) method is low while the 2-dimensional method of co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both of which can limit the future clinical application of hESC-ECs. Moreover, to fully understand the beneficial effects of stem cell therapy, investigators must be able to track the functional biology and physiology of transplanted cells in living subjects over time.
In this study, we developed an extracellular matrix (ECM) culture system for increasing endothelial differentiation and free from contaminating animal cells. We investigated the transcriptional changes that occur during endothelial differentiation of hESCs using whole genome microarray, and compared to human umbilical vein endothelial cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a mouse dorsal window model. Moreover, our study is the first so far to transplant hESC-ECs in a myocardial infarction model and monitor cell fate using molecular imaging methods.
Taken together, we report a more efficient method for derivation of hESC-ECs that express appropriate patterns of endothelial genes, form functional vessels in vivo, and improve cardiac function. These studies suggest that hESC-ECs may provide a novel therapy for ischemic heart disease in the future.
人类胚胎干细胞分化为内皮细胞（hESC-ECs）有潜力通过支持血管生成和血管发生为缺血性疾病的新型移植治疗提供无限的细胞来源。然而，传统胚状体（EB）方法的内皮分化效率低，而与小鼠胚胎成纤维细胞（MEFs）共培养的 2 维方法需要动物产品，这两者都可能限制 hESC-ECs 的未来临床应用。此外，为了充分了解干细胞治疗的有益效果，研究人员必须能够在活体动物中随时间跟踪移植细胞的功能生物学和生理学。
在这项研究中，我们开发了一种无动物细胞污染的细胞外基质（ECM）培养系统，以提高内皮分化效率。我们使用全基因组微阵列研究了 hESC 内皮分化过程中的转录变化，并与人脐静脉内皮细胞（HUVECs）进行了比较。我们还展示了 hESC-ECs 在小鼠背窗模型中的功能性血管形成。此外，我们的研究是迄今为止首次在心肌梗死模型中移植 hESC-ECs 并使用分子成像方法监测细胞命运的研究。
综上所述，我们报告了一种更有效的 hESC-ECs 诱导方法，该方法表达适当的内皮基因模式，在体内形成功能性血管，并改善心脏功能。这些研究表明，hESC-ECs 可能为未来的缺血性心脏病提供一种新的治疗方法。
