Gene expression profiling and evaluation of physiologic functions in monocyte-derived multipotential cells

我们最近发现了一种新的CD14^+ CD45^+ CD34^+ I型胶原^+细胞组分，来源于人类循环CD14^+单核细胞，单核细胞衍生多能细胞（MOMC），其包含能够分化为各种间充质细胞的祖细胞，包括骨、软骨、脂肪和骨骼肌。为了鉴定可能参与多电位的momc相关基因，通过基因芯片分析比较了循环单核细胞和momc之间的基因表达谱。6个基因，包括DLG3、MyoX、SEPT3、EFNA3、ATF-1和SAP30，被鉴定为单核细胞谱系细胞类型中MOMC中优先表达的基因。接下来，将人momc与大鼠心肌细胞或神经元的原代培养物共同培养，分别表达心肌细胞或神经元特异性转录因子和结构蛋白。momc衍生的心肌细胞样细胞表现出自发跳动，并表现出心室肌细胞的电生理特性。经血管生成因子处理的momc在形态上发生了变化，内皮特异性分子的表达呈尾状和上调。momc衍生内皮细胞和成熟内皮细胞的功能特征无法区分。在使用SCID小鼠模型的异种移植研究中，在同基因结肠癌中皮下注射人momc，与momc共移植显着促进血管形成。超过50%的血管含有人momc来源的内皮细胞。最后，momc能够在体外2周内将人造血干细胞扩增到100倍，但不能维持长期培养启动细胞。与目前提出的使用组织特异性干细胞和胚胎干细胞的策略相比，使用momc的细胞治疗具有相当大的优势。循环单核细胞可以成为自体细胞移植用于组织再生的丰富且易于获取的来源，并且可以绕过使用胚胎干细胞的伦理困境。我们的研究结果表明，使用momc的策略可以成为基于干细胞的再生疗法的实用替代方案之一。少

We have recently identified a novel CD14^+ CD45^+ CD34^+ type I collagen^+ cell fraction derived from human circulating CD14^+ monocytes, monocyte-derived multipotential cell (MOMC), which contains progenitors capable of differentiating into a variety of mesenchymal cells, including bone, cartilage, fat and skeletal muscle. To identify MOMC-related genes potentially involved in multipotentiality, gene expression profiling was compared between circulating monocytes and MOMCs by genechip analysis. Six genes, including DLG3, MyoX, SEPT3, EFNA3, ATF-1, and SAP30, were identified as genes preferentially expressed in the MOMC among monocyte-lineage cell types. Next, human MOMCs co-cultivated with primary cultures of rat cardiomyocytes or neurons underwent expression of cardiomyocyte- or neuron-specific transcription factors and structural proteins, respectively. MOMC-derived cardiomyocyte-like cells represented spontaneously beating, and exhibited electrophysiological properties of ventricul … More ar myocytes. MOMCs treated with angiogenic factors underwent a change in their morphology to caudated and upregulated expression of endothelium-specific molecules. Functional characteristics were indistinguishable between MOMC-derived endothelial cells and mature endothelial cells. In xenogenic transplantation studies using a SCID mouse model, in which syngeneic colon carcinoma were injected subcutaneously with human MOMCs, co-transplantation with MOMCs markedly promoted blood vessel formation. More than 50% of blood vessels incorporated human MOMC-derived endothelial cells. Finally, MOMCs were able to expand human hematopoietic stem cells to 100-fold in vitro in 2 weeks, but failed to maintain longterm-culture-initiating cells.The cellular therapy using MOMCs has considerable advantages over currently proposed strategies using tissue-specific stem cells and embryonic stem cells. Circulating monocytes can be an abundant and easily accessible source for autologous cell transplantation for tissue regeneration, and the ethical dilemma of using ES cells can be bypassed. Our findings suggest that strategies to use MOMCs can be one of practical alternatives to the stem cell-based regenerative therapies. Less