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

单核细胞来源的多能细胞的基因表达谱和生理功能评估

基本信息

批准号：
15390307
负责人：
KUWANA Masataka
金额：
$ 9.54万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390307/
关键词：
Regenerative medicine Monocyte Differentiation Trans-differentiation Stem cell Genechip 遣伝子チップ心筋神経

项目摘要

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

我们最近发现了一种新型 CD14^+ CD45^+ CD34^+ I 型胶原^+ 细胞组分，源自人类循环 CD14^+ 单核细胞，即单核细胞衍生的多能细胞 (MOMC)，其中含有能够分化为多种细胞的祖细胞。间充质细胞，包括骨、软骨、脂肪和骨骼肌，为了识别可能参与多能性的 MOMC 相关基因，对循环之间的基因表达谱进行了比较。通过基因芯片分析，包括 DLG3、MyoX、SEPT3、EFNA3、ATF-1 和 SAP30 在内的 6 个基因被鉴定为在单核细胞谱系细胞类型中优先表达的基因。大鼠心肌细胞或神经元的原代培养物分别表达心肌细胞或神经元特异性转录因子和 MOMC 衍生的心肌细胞样细胞。 MOMC 来源的内皮细胞和成熟内皮细胞之间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，其中同基因结肠癌皮下注射人 MOMC，与MOMCs共移植显着促进了血管形成，超过50%的血管融入了人类MOMC衍生的内皮细胞，最终，MOMCs能够在体外将人类造血干细胞扩增至100倍，但未能成功。维持长期培养起始细胞。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 的细胞疗法具有相当大的优势。且易于获得用于组织再生的自体细胞移植来源，并且可以绕过使用 ES 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。