胎儿和成人骨髓间充质干细胞体外造血支持能力的比较(英文)

Comparison of Hematopoietic Supportive Capacity between Human Fetal and Adult Bone Marrow Mesenchymal Stem Cells In Vitro

胎儿出生以后,造血干细胞(HSC)才从胎儿的肝脏和脾脏转移到骨髓,这一过程可能由不同的造血微环境中的信号分子所介导。间充质干细胞(MSC)是骨髓微环境中间质细胞如成骨细胞、内皮细胞的前体祖细胞。研究者推测,胎儿出生前的骨髓可能并不特别适合HSC生长。然而,该假说尚缺乏直接的证据支持。本研究通过对胎儿和成人骨髓MSC的造血支持能力进行比较,拟为此提供证据。成人骨髓MSC来源于3位健康供者,胎儿骨髓MSC来源于孕19-20周流产的胎儿。MSC辐照后与CD34+一起进行长期培养启动细胞分析,计数克隆形成细胞的数量,流式分析培养后CD34+的表型变化。RT-PCR分析两种MSC中细胞因子的表达。结果显示,成人骨髓MSC比胎儿骨髓MSC具有更强的造血支持能力,两者都促进CD34+向髓系细胞分化,两者之间细胞因子的表达存在差异。结论:与胎儿骨髓MSC相比,成人骨髓MSC在某些治疗,尤其是促进造血恢复方面具有更广泛的应用前景。

Hematopoietic stem cells （HSC） shift from fetal liver and spleen to bone marrow at neonatal stages and this movement may be due to inductive signals from different microenviroments. Mesenchymal stem cells （MSC） are the precursors of stromal cells in bone marrow microenviroments such as osteoblasts and endothelial cells. Some researchers speculated that fetal bone marrow before birth might be not perfectly suit HSC growth. However, it is still lack of direct evidence to prove this hypothesis. This study was aimed to compare the hematopoietic supportive capacity between human fetal and adult bone marrow MSC in vitro. Adult bone marrow MSC （ABM-MSC） were isolated from three healthy donors and fetal bone marrow MSC （FBM-MSC） were isolated from three fetuses between gestations of 19 to 20 weeks. After irradiation, MSC were co-cultured with CD34＋ cells isolated from umbilical cord blood in long-term culture-initiating cell （LTC-IC） assay. The colony number of colony forming cells （CFC） was counted and the phenotypic changes of co-cultured CD34＋ cells were analyzed by flow cytometry. Cytokine expressions in both kinds of MSC were detected by reverse transcription polymerase chain reaction （RT-PCR）. The results showed that ABM-MSC had a stronger hematopoietic supportive capacity than FBM-MSC. Both of them enhanced the differentiation of CD34＋ cells into myeloid lineages. Cytokines were expressed differently in ABM-MSC and FBM-MSC. It is concluded that ABM- MSC possess more potential application in some treatments than FBM-MSC, especially in hematopoietic reconstitution.