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羊水来源的多能间充质基质细胞:临床应用的可靠前景

Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application.

作者信息

Sessarego Nadia, Parodi Alessia, Podestà Marina, Benvenuto Federica, Mogni Massimo, Raviolo Valentina, Lituania Mario, Kunkl Annalisa, Ferlazzo Guido, Bricarelli Franca Dagna, Uccelli Antonio, Frassoni Francesco

机构信息

Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, L.go R. Benzi 10, 16132 Genova Italy.

出版信息

Haematologica. 2008 Mar;93(3):339-46. doi: 10.3324/haematol.11869. Epub 2008 Feb 11.

Abstract

BACKGROUND

Mesenchymal stromal cells are multipotent cells considered to be of great promise for use in regenerative medicine. However, the cell dose may be a critical factor in many clinical conditions and the yield resulting from the ex vivo expansion of mesenchymal stromal cells derived from bone marrow may be insufficient. Thus, alternative sources of mesenchymal stromal cells need to be explored. In this study, mesenchymal stromal cells were successfully isolated from second trimester amniotic fluid and analyzed for chromosomal stability to validate their safety for potential utilization as a cell therapy product.

DESIGN AND METHODS

Mesenchymal stromal cells were expanded up to the sixth passage starting from amniotic fluid using different culture conditions to optimize large-scale production.

RESULTS

The highest number of mesenchymal stromal cells derived from amniotic fluid was reached at a low plating density; in these conditions the expansion of mesenchymal stromal cells from amniotic fluid was significantly greater than that of adult bone marrow-derived mesenchymal stromal cells. Mesenchymal stromal cells from amniotic fluid represent a relatively homogeneous population of immature cells with immunosuppressive properties and extensive proliferative potential. Despite their high proliferative capacity in culture, we did not observe any karyotypic abnormalities or transformation potential in vitro nor any tumorigenic effect in vivo.

CONCLUSIONS

Fetal mesenchymal stromal cells can be extensively expanded from amniotic fluid, showing no karyotypic abnormalities or transformation potential in vitro and no tumorigenic effect in vivo. They represent a relatively homogeneous population of immature mesenchymal stromal cells with long telomeres, immunosuppressive properties and extensive proliferative potential. Our results indicate that amniotic fluid represents a rich source of mesenchymal stromal cells suitable for banking to be used when large amounts of cells are required.

摘要

背景

间充质基质细胞是多能细胞,被认为在再生医学中具有巨大的应用前景。然而,细胞剂量在许多临床情况下可能是一个关键因素,并且从骨髓中获取的间充质基质细胞体外扩增所得到的产量可能不足。因此,需要探索间充质基质细胞的替代来源。在本研究中,成功从孕中期羊水分离出间充质基质细胞,并对其进行染色体稳定性分析,以验证其作为细胞治疗产品潜在应用的安全性。

设计与方法

使用不同培养条件从羊水开始将间充质基质细胞扩增至第六代,以优化大规模生产。

结果

在低接种密度下,从羊水中获得的间充质基质细胞数量最多;在这些条件下,羊水来源的间充质基质细胞的扩增明显大于成人骨髓来源的间充质基质细胞。羊水来源的间充质基质细胞代表了一群相对均一的未成熟细胞,具有免疫抑制特性和广泛的增殖潜力。尽管它们在培养中具有高增殖能力,但我们在体外未观察到任何核型异常或转化潜能,在体内也未观察到任何致瘤作用。

结论

胎儿间充质基质细胞可从羊水中大量扩增,在体外未显示核型异常或转化潜能,在体内也无致瘤作用。它们代表了一群相对均一的未成熟间充质基质细胞,具有长端粒、免疫抑制特性和广泛的增殖潜力。我们的结果表明,羊水是间充质基质细胞的丰富来源,适合储存,以便在需要大量细胞时使用。

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