Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Bio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stem Cell Reports. 2016 Jan 12;6(1):95-108. doi: 10.1016/j.stemcr.2015.11.006.
The generation of tissue-specific cell types from human embryonic stem cells (hESCs) is critical for the development of future stem cell-based regenerative therapies. Here, we identify CD13 and ROR2 as cell-surface markers capable of selecting early cardiac mesoderm emerging during hESC differentiation. We demonstrate that the CD13+/ROR2+ population encompasses pre-cardiac mesoderm, which efficiently differentiates to all major cardiovascular lineages. We determined the engraftment potential of CD13+/ROR2+ in small (murine) and large (porcine) animal models, and demonstrated that CD13+/ROR2+ progenitors have the capacity to differentiate toward cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells in vivo. Collectively, our data show that CD13 and ROR2 identify a cardiac lineage precursor pool that is capable of successful engraftment into the porcine heart. These markers represent valuable tools for further dissection of early human cardiac differentiation, and will enable a detailed assessment of human pluripotent stem cell-derived cardiac lineage cells for potential clinical applications.
从人类胚胎干细胞 (hESC) 中生成组织特异性细胞类型对于未来基于干细胞的再生疗法的发展至关重要。在这里,我们确定 CD13 和 ROR2 是能够选择在 hESC 分化过程中出现的早期心脏中胚层的细胞表面标志物。我们证明 CD13+/ROR2+ 群体包含心脏前中胚层,它能够有效地分化为所有主要的心血管谱系。我们确定了 CD13+/ROR2+ 在小型(鼠)和大型(猪)动物模型中的植入潜力,并证明 CD13+/ROR2+ 祖细胞具有向心肌细胞、成纤维细胞、平滑肌和内皮细胞分化的能力。总的来说,我们的数据表明 CD13 和 ROR2 鉴定了一个心脏谱系前体池,能够成功植入猪心脏。这些标志物代表了进一步解析早期人类心脏分化的有价值的工具,并将能够对潜在临床应用的人类多能干细胞衍生的心脏谱系细胞进行详细评估。
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