Functional Module Analysis Reveals Differential Osteogenic and Stemness Potentials in Human Mesenchymal Stem Cells from Bone Marrow and Wharton's Jelly of Umbilical Cord
Functional Module Analysis Reveals Differential Osteogenic and Stemness Potentials in Human Mesenchymal Stem Cells from Bone Marrow and Wharton's Jelly of Umbilical Cord
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DOI：
10.1089/scd.2009.0485
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发表时间：
2010-12-01
影响因子：
4
通讯作者：
Wang, Hsei-Wei
中科院分区：
文献类型：
--
作者：
Hsieh, Jui-Yu;Fu, Yu-Show;Wang, Hsei-Wei
骨髓间充质干细胞（MSC）是一种有吸引力的损伤组织再生来源。替代的出生后，围产期和胎儿来源的MSC也在深入调查。脐带间充质干细胞（WJ）的华顿氏胶质基质间充质干细胞具有较高的胰腺和内皮细胞分化潜能比BM-MSCs，但其潜在的机制知之甚少。我们比较了BM-MSCs和WJ-MSCs的基因表达谱、丰富的经典途径和遗传网络。WJ-MSCs表达更多的血管生成和生长相关基因，包括表皮生长因子和FLT 1，而BM-MSCs表达更多的成骨基因，如RUNX 2，DLX 5和NPR 3。BM-MSCs的基因表达模式比WJ-MSCs更接近于成骨细胞，提示其具有更好的成骨潜能。相比之下，WJ-MSCs更原始，因为它们与胚胎干细胞共享更多共同的基因。BM-MSCs对环境刺激更敏感，因为它们的分子特征在不同的培养条件下改变更显著。WJ-MSC表达富含血管内皮生长因子和PI 3 K-NF κ B经典途径的基因，而BM-MSC表达涉及抗原呈递和趋化因子/细胞因子途径的基因。干实验室结果可以通过湿实验室实验来验证，其中BM-MSCs在成骨和成脂分化中更有效，而WJ-MSCs增殖更好。因此，WJ-MSCs构成血管生成的一个有前途的选择，而BM-MSCs在骨重建。我们的研究结果系统地揭示了来自独特的本体和解剖学来源的2种MSC的潜在基因和调控网络，以及由此产生的表型，从而为基于细胞的治疗和以下MSC生物学机制研究提供了更好的基础。
Mesenchymal stem cells (MSCs) found in bone marrow (BM)-MSCs are an attractive source for the regeneration of damaged tissues. Alternative postnatal, perinatal, and fetal sources of MSCs are also under intensive investigation. MSCs from the Wharton's jelly matrix of umbilical cord (WJ)-MSCs have higher pancreatic and endothelial differentiation potentials than BM-MSCs, but the underlying mechanisms are poorly understood. We compared the gene expression profiles, enriched canonical pathways, and genetic networks of BM-MSCs and WJ-MSCs. WJ-MSCs express more angiogenesis-and growth-related genes including epidermal growth factor and FLT1, whereas BM-MSCs express more osteogenic genes such as RUNX2, DLX5, and NPR3. The gene expression pattern of BM-MSCs is more similar to osteoblasts than WJ-MSCs, suggesting a better osteogenic potential. In contrast, WJ-MSCs are more primitive because they share more common genes with embryonic stem cells. BM-MSCs are more sensitive to environmental stimulations because their molecular signatures altered more significantly in different culture conditions. WJ-MSCs express genes enriched in vascular endothelial growth factor and PI3K-NF kappa B canonical pathways, whereas BM-MSCs express genes involved in antigen presentation and chemokine/cytokine pathways. Drylab results could be verified by wetlab experiments, in which BM-MSCs were more efficient in osteogenic and adipogenic differentiation, whereas WJ-MSCs proliferated better. WJ-MSCs thus constitute a promising option for angiogenesis, whereas BM-MSCs in bone remodeling. Our results reveal systematically the underlying genes and regulatory networks of 2 MSCs from unique ontological and anatomical origins, as well as the resulted phenotypes, thereby providing a better basis for cell-based therapy and the following mechanistic studies on MSC biology.