多区域人间质血管细胞:多能性和干细胞特性。

Multidistrict human mesenchymal vascular cells: pluripotency and stemness characteristics.

机构信息

Clinical and Surgical Pathology, Department of Radiological and Histocytopathological Clinical Sciences, S. Orsola Hospital, University of Bologna, Bologna, Italy.

出版信息

Cytotherapy. 2010 May;12(3):275-87. doi: 10.3109/14653241003596679.

Abstract

BACKGROUND AIMS

The presence of ectopic tissues in the pathologic artery wall raises the issue of whether multipotent stem cells may reside in the vasculature itself. Recently mesenchymal stromal cells (MSC) have been isolated from different human vascular segments (VW MSC), belying the previous view that the vessel wall is a relatively quiescent tissue.

METHODS

Resident multipotent cells were recovered from fresh arterial segments (aortic arches, thoracic and femoral arteries) collected in a tissue-banking facility and used to establish an in situ and in vitro study of the stemness features and multipotency of these multidistrict MSC populations.

RESULTS

Notch-1+, Stro-1+, Sca-1+ and Oct-4+ cells were distributed along an arterial wall vasculogenic niche. Multidistrict VW MSC homogeneously expressed markers of stemness (Stro-1, Notch-1 and Oct-4) and MSC lineages (CD44, CD90, CD105, CD73, CD29 and CD166) whilst they were negative for hematopoietic and endothelial markers (CD34, CD45, CD31 and vWF). Each VW MSC population had characteristics of stem cells, i.e. a high efflux capability for Hoechst 33342 dye and the ability to form spheroids when grown in suspension and generate colonies when seeded at low density. Again, VW MSC cultured in induction media exhibited adipogenic, chondrogenic and leiomyogenic potential but less propensity to osteogenic differentiation, as documented by histochemical, immunohistochemical, molecular and electron microscopy analysis.

CONCLUSIONS

Overall, these findings may enlighten the physiopathologic mechanisms of vascular wall diseases as well as having potential implications for cellular, genetic and tissue engineering approaches to treating vascular pathologies when these are unresponsive to medical and surgical therapies.

摘要

背景目的

异位组织在病变动脉壁中的存在提出了一个问题,即多能干细胞是否可能存在于血管本身中。最近,间充质基质细胞(MSC)已从不同的人血管段(VW MSC)中分离出来,这颠覆了以前认为血管壁是一种相对静止组织的观点。

方法

从组织库中收集的新鲜动脉段(主动脉弓、胸和股动脉)中回收驻留的多能细胞,并用于建立这些多区 VW MSC 群体的干性特征和多能性的原位和体外研究。

结果

Notch-1+、Stro-1+、Sca-1+和 Oct-4+细胞沿动脉壁血管生成龛分布。多区 VW MSC 均匀表达干性标志物(Stro-1、Notch-1 和 Oct-4)和 MSC 谱系标志物(CD44、CD90、CD105、CD73、CD29 和 CD166),而它们对造血和内皮标志物(CD34、CD45、CD31 和 vWF)呈阴性。每个 VW MSC 群体都具有干细胞的特征,即 Hoechst 33342 染料的高外排能力,以及在悬浮培养时形成球体的能力,并且在低密度接种时能够形成集落。同样,VW MSC 在诱导培养基中培养时表现出成脂、成软骨和成肌潜能,但成骨分化倾向较低,组织化学、免疫组织化学、分子和电子显微镜分析证明了这一点。

结论

总的来说,这些发现可能阐明了血管壁疾病的病理生理机制,并且当这些疾病对药物和手术治疗无反应时,对细胞、遗传和组织工程方法治疗血管病变具有潜在意义。

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