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基质细胞衍生因子 1-α与 BMP-2 和 TGF-β1 联合诱导靶向细胞归巢和骨与软骨分化,用于组织工程,无需细胞接种。

Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding.

机构信息

Department of Plastic Surgery, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.

出版信息

Cell Tissue Res. 2012 Oct;350(1):89-94. doi: 10.1007/s00441-012-1449-x. Epub 2012 Jun 12.

Abstract

The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient's own cells to an implanted scaffold through controlled delivery of cytokines. In this study, we used stromal-cell-derived factor 1-alpha (SDF-1α) in combination with bone morphogenic protein (BMP)-2 or transforming growth factor (TGF)-β1 to induce cell migration and osteogenic or chondrogenic differentiation, respectively, in implanted scaffolds in a rat model. A customized cytokine microdelivery apparatus was used to ensure the constant rate and concentration of cytokine delivery around the scaffold. The formation of osteoid or early cartilage was observed after 4 weeks in specimens treated with SDF-1α and either BMP-2 or TGF-β1. The density of cellular infiltrate and formation of differentiated tissue were lower in scaffolds treated only with BMP-2 or TGF-β1. Thus, controlled SDF-1α delivery induces cell migration into scaffolds and can result in enhanced osteogenesis and chondrogenesis when used in combination with differentiation cytokines for purposes of tissue engineering.

摘要

组织工程方法的临床转化受到细胞来源的要求限制。细胞导向是一个新概念,它提供了一种替代方法,避免了对外部细胞来源的需求。这依赖于通过细胞因子的受控递送来实现患者自身细胞的特定部位归巢和分化到植入的支架上。在这项研究中,我们在大鼠模型中使用基质细胞衍生因子 1-α(SDF-1α)与骨形态发生蛋白(BMP)-2 或转化生长因子(TGF)-β1 联合使用,分别诱导植入支架中的细胞迁移和成骨或软骨分化。定制的细胞因子微输送装置用于确保支架周围细胞因子输送的恒定速率和浓度。在用 SDF-1α 处理的标本中,在 4 周后观察到骨样或早期软骨的形成,同时用 BMP-2 或 TGF-β1 处理。仅用 BMP-2 或 TGF-β1 处理的支架中的细胞浸润密度和分化组织的形成较低。因此,受控 SDF-1α 递送至支架中可诱导细胞迁移,并在与分化细胞因子联合使用时,增强组织工程中的成骨和软骨形成。

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