比较分析脐血和其他来源的人骨髓间充质基质细胞的成脂潜能。

A comparative analysis of the adipogenic potential in human mesenchymal stromal cells from cord blood and other sources.

机构信息

Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.

出版信息

Cytotherapy. 2013 Jan;15(1):76-88. doi: 10.1016/j.jcyt.2012.11.001.

Abstract

BACKGROUND AIMS

Mesenchymal stromal cells (MSCs) from umbilical cord blood (CB) attract attention by significantly impaired or absent adipogenic differentiation compared with MSCs derived from bone marrow (BM) and adipose tissue (AT). The diverging adipogenic propensity between the developmentally younger CB-MSCs and MSCs of the adult AT and BM resembles the age-dependent process in the BM, where adipose tissue increases with advancing age, accompanied by loss of bone stability. Thus, MSCs appeal as an attractive model to study the adipogenic process with respect to tissue sources and developmental ages.

METHODS

We followed the expression of main adipogenic transcription factors, genes and protein markers in CB-, BM- and AT-MSCs under adipogenic induction, after silencing of preadipocyte factor 1 (Pref-1, PREF1) and after incubation with CB-plasma supplemented adipogenic media.

RESULTS

An inverse relation in the expression of adipogenesis-associated markers and PREF1 in CB-MSCs suggested an inhibitory role of Pref-1 toward adipogenesis. However, Pref-1 protein was rarely detected in CB-MSCs, and siRNA silencing of Pref-1 failed to induce adipogenic differentiation in CB-MSCs. Thus, the impaired adipogenic differentiation of CB-MSCs in vitro was unrelated to endogenous Pref-1 protein expression. Nevertheless CB-plasma containing Pref-1 protein revealed an anti-adipogenic effect on AT-MSCs.

CONCLUSIONS

Because Pref-1 is vastly abundant in CB-plasma and confers anti-adipogenic properties, Pref-1 in association with the ontogenic milieu probably induces long-lasting unresponsiveness toward adipogenic stimuli in CB-MSCs.

摘要

背景目的

与骨髓(BM)和脂肪组织(AT)来源的间充质基质细胞(MSCs)相比,脐血(CB)来源的 MSCs 脂肪生成分化能力显著受损或缺失,因此备受关注。CB-MSCs 的脂肪生成倾向与 AT 和 BM 中 MSC 的发育年龄存在差异,这类似于 BM 中年龄依赖性的过程,即随着年龄的增长,脂肪组织增加,同时伴随着骨稳定性的丧失。因此,MSCs 作为一种有吸引力的模型,可用于研究组织来源和发育年龄对脂肪生成过程的影响。

方法

我们在诱导脂肪生成后,观察 CB-MSCs、BM-MSCs 和 AT-MSCs 中主要脂肪生成转录因子、基因和蛋白标志物的表达情况,在沉默前脂肪细胞因子 1(Pref-1,PREF1)后,以及在补充 CB 血浆的脂肪生成培养基中孵育后,观察这些标志物的表达情况。

结果

CB-MSCs 中脂肪生成相关标志物和 PREF1 的表达呈负相关,表明 Pref-1 对脂肪生成具有抑制作用。然而,CB-MSCs 中很少检测到 Pref-1 蛋白,并且 siRNA 沉默 Pref-1 并不能诱导 CB-MSCs 向脂肪细胞分化。因此,CB-MSCs 体外脂肪生成分化受损与内源性 Pref-1 蛋白表达无关。然而,含有 Pref-1 蛋白的 CB 血浆对 AT-MSCs 表现出抗脂肪生成作用。

结论

由于 Pref-1 在 CB 血浆中含量丰富,并具有抗脂肪生成特性,因此 Pref-1 可能与个体发生环境一起,诱导 CB-MSCs 对脂肪生成刺激产生持久的无反应性。

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