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全面的人类骨髓间充质干细胞特征研究,重点在于分子和超微结构特性。

A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties.

机构信息

Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University, Kocaeli, Turkey.

出版信息

J Cell Physiol. 2011 May;226(5):1367-82. doi: 10.1002/jcp.22468.

Abstract

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) continue to draw attention of researchers in the fields of basic science and medicine due to their indispensible regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties, all of which collectively point out their enormous therapeutic potential. There is still, however, a need for further investigation of their characteristics to broaden their field of use and learn much more about how to control their fate and improve their therapeutic effectiveness. hBM-MSCs were extensively characterized in terms of their growth characteristics, genetic stability, and differentiation capability to the mesodermal and ectodermal cell lineages; a special emphasis was given to their phenotypic and ultrastructural properties. Expression of embryonic stem cell markers Oct4, Rex-1, FoxD-3, Sox2, and Nanog was shown with real-time PCR. Transmission electron microscopy revealed the ultrastructural characteristics of hBM-MSCs; they had pale, irregularly shaped and large euchromatic nuclei, and two distinct areas in their cytoplasm: an intensely stained inner zone rich in mitochondria and rough endoplasmic reticulum (rER) with dilated cisternae and a relatively peripheral zone poor in organelles. hBM-MSCs expressed adipogenic (adipophilin and PPARγ), myogenic (desmin, myogenin, α-SMA), neurogenic (γ-enolase, MAP2a,b, c-fos, nestin, NF-H, NF-L, GFAP, β3-tubulin), osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, type I collagen), and chondrogenic (type II collagen, SOX9) markers either at RNA or protein level even under basal conditions, without any stimulation towards differentiation. The differentiation potential of hBM-MSCs to adipogenic, osteogenic, and neurogenic lineages was shown by using the relevant differentiation factors.

摘要

人骨髓间充质干细胞(hBM-MSCs)因其不可或缺的再生、修复、血管生成、抗凋亡和免疫抑制特性,继续引起基础科学和医学领域研究人员的关注,所有这些特性共同指出其巨大的治疗潜力。然而,仍然需要进一步研究其特性,以扩大其应用领域,并更多地了解如何控制其命运和提高其治疗效果。hBM-MSCs 在生长特性、遗传稳定性和向中胚层和外胚层细胞谱系的分化能力方面得到了广泛的描述;特别强调了它们的表型和超微结构特性。实时 PCR 显示了胚胎干细胞标志物 Oct4、Rex-1、FoxD-3、Sox2 和 Nanog 的表达。透射电镜显示了 hBM-MSCs 的超微结构特征;它们具有浅而不规则形状的大常染色质核,以及细胞质中的两个不同区域:富含线粒体和粗面内质网(rER)的染色强烈的内区,其小泡扩张,以及相对细胞器较少的周边区。hBM-MSCs 表达脂肪生成(脂联素和 PPARγ)、肌生成(结蛋白、肌生成素、α-SMA)、神经生成(γ-烯醇化酶、MAP2a、b、c-fos、巢蛋白、NF-H、NF-L、GFAP、β3-微管蛋白)、成骨(骨连蛋白、骨钙素、骨桥蛋白、Runx-2、I 型胶原)和软骨生成(II 型胶原、SOX9)标志物,无论是在 RNA 还是蛋白质水平,甚至在没有任何分化刺激的情况下也是如此。通过使用相关的分化因子,显示了 hBM-MSCs 向脂肪生成、成骨和神经生成谱系的分化潜力。

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