Comparative Transcriptome Analysis of Mesenchymal Stem Cells Derived from Bone Marrow and Wharton’s Jelly of Umbilical Cord

• Main Authors: Jui-Yu Hsieh, 謝睿瑜
• Other Authors: Hsei-Wei Wang
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/36849809033388474398

博士 === 國立陽明大學 === 微生物及免疫學研究所 === 101 === Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases because of their differentiating abilities and their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. Here, we aim to understand the functional comparison of WJ-MSCs with MSC from bone marrow (BM-MSCs) and to identify molecular regulation involved in MSC phenotypes. First, the gene expression patterns and genetic networks of BM-MSCs and WJ-MSCs were compared. BM-MSCs expressed more genes related to skeletal development, while WJ-MSCs express more growth-related genes. WJ-MSCs are more primitive since they share more common genes with embryonic stem cells. Drylab results could be verified by wetlab experiments, in which BM-MSCs were more efficient in osteogenic and adipogenic differentiation, while WJ-MSCs proliferated faster. Second, we compared the secretomes of BM-MSCs and WJ-MSCs, and found that WJ-MSCs express more secreted factors related to angiogenesis and neurogenesis. Functional assays showed that WJ-MSCs induced better neural differentiation and neural cell migration. WJ-MSCs had superior neuropeotective effects on primary cortical cells injured by oxygen-glucose deprivation culture. WJ-MSC secreted factors also induced better microvasculature formation and cell migration on co-cultured endothelial cells. Third, since the migration of transplanted MSCs to injured sites is also a critical property of engraftment, our aim was to identify critical miRNAs controlling MSCs proliferation and migration. WJ-MSCs showed poorer motility and better proliferation ability compared to BM-MSCs. Small RNA sequencing revealed that miR-146a-5p is significantly overexpressed in WJ-MSCs with high abundance. Knockdown of miR-146a-5p in WJ-MSCs inhibited their proliferation yet enhanced their migration. CXCL12, together with SIKE1, which is an IKKε suppressor, are direct targets of miR-146a-5p in MSCs. miR-146a-5p is also downstream of CXCL12, and a negative feedback loop is therefore formed in MSCs. Our study provides the basis for the development of cell-based therapy and the transcriptomic results also reveals of follow-up mechanistic studies related to MSC biology.