Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Medical Center, Duesseldorf, Germany.
Stem Cells Dev. 2010 Oct;19(10):1471-83. doi: 10.1089/scd.2010.0070.
In addition to hematopoietic stem cells, cord blood (CB) also contains different nonhematopoietic CD45-, CD34- adherent cell populations: cord blood mesenchymal stromal cells (CB MSC) that behave almost like MSC from bone marrow (BM MSC) and unrestricted somatic stem cells (USSC) that differentiate into cells of all 3 germ layers. Distinguishing between these populations is difficult due to overlapping features such as the immunophenotype or the osteogenic and chondrogenic differentiation pathway. Functional differences in the differentiation potential suggest different developmental stages or different cell populations. Here we demonstrate that the expression of genes and the differentiation toward the adipogenic lineage can discriminate between these 2 populations. USSC, including clonal-derived cells lacking adipogenic differentiation, strongly expressed δ-like 1/preadipocyte factor 1 (DLK-1/PREF1) correlating with high proliferative potential, while CB MSC were characterized by a strong differentiation toward adipocytes correlating with a weak or negative DLK-1/PREF1 expression. Constitutive overexpression of DLK-1/PREF1 in CB MSC resulted in a reduced adipogenic differentiation, whereas silencing of DLK-1 in USSC resulted in adipogenic differentiation.
除了造血干细胞,脐带血 (CB) 中还含有不同的非造血性 CD45-、CD34- 贴壁细胞群:脐带血间充质基质细胞 (CB MSC),其行为几乎与骨髓 (BM MSC) 中的间充质基质细胞相同,以及无限制的体干细胞 (USSC),其可以分化为所有 3 个胚层的细胞。由于免疫表型或成骨和成软骨分化途径等重叠特征,区分这些群体比较困难。功能上分化潜能的差异表明不同的发育阶段或不同的细胞群体。在这里,我们证明了基因表达和向脂肪生成谱系的分化可以区分这两个群体。包括缺乏脂肪生成分化的克隆衍生细胞在内的 USSC,强烈表达类似于 1/前脂肪细胞因子 1 (DLK-1/PREF1),与高增殖潜能相关,而 CB MSC 的特征是向脂肪细胞强烈分化,与低或负的 DLK-1/PREF1 表达相关。CB MSC 中 DLK-1/PREF1 的组成性过表达导致脂肪生成分化减少,而 USSC 中 DLK-1 的沉默导致脂肪生成分化。