title: Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells.
abstract: Transplantation of mesenchymal stem cells (MSCs) has been used to treat a wide range of diseases, and the mechanism of action is postulated to be mediated by either differentiation into functional reparative cells that replace injured tissues or secretion of paracrine factors that promote tissue repair. To complement earlier studies that identified some of the paracrine factors, we profiled the paracrine proteome to better assess the relevance of MSC paracrine factors to the wide spectrum of MSC-mediated therapeutic effects. To evaluate the therapeutic potential of the MSC paracrine proteome, a chemically defined serum-free culture medium was conditioned by MSCs derived from human embryonic stem cells using a clinically compliant protocol. The conditioned medium was analyzed by multidimensional protein identification technology and cytokine antibody array analysis and revealed the presence of 201 unique gene products. 86-88% of these gene products had detectable transcript levels by microarray or quantitative RT-PCR assays. Computational analysis predicted that these gene products will significantly drive three major groups of biological processes: metabolism, defense response, and tissue differentiation including vascularization, hematopoiesis, and skeletal development. It also predicted that the 201 gene products activate important signaling pathways in cardiovascular biology, bone development, and hematopoiesis such as Jak-STAT, MAPK, Toll-like receptor, transforming growth factor-beta, and mTOR (mammalian target of rapamycin) signaling pathways. This study identified a large number of MSC secretory products that have the potential to act as paracrine modulators of tissue repair and replacement in diseases of the cardiovascular, hematopoietic, and skeletal tissues. Moreover our results suggest that human embryonic stem cell-derived MSC-conditioned medium has the potency to treat a variety of diseases in humans without cell transplantation.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Ruenn Chai
authors.initials: RC
authors.lastname: Lai
authors.forename: Eileen
authors.initials: E
authors.lastname: Khia Way Tan
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Keng Suan
authors.initials: KS
authors.lastname: Yeo
authors.forename: Teck Yew
authors.initials: TY
authors.lastname: Low
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
authors.forename: Chuen Neng
authors.initials: CN
authors.lastname: Lee
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitchell
authors.forename: Reida Menshawe
authors.initials: RM
authors.lastname: El Oakley
authors.forename: Sai-Kiang
authors.initials: SK
authors.lastname: Lim
mesh_terms: D002853:Chromatography, Liquid; D017077:Culture Media, Conditioned; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D040081:Protein Array Analysis; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D017077:Culture Media, Conditioned; D020543:Proteome; D012333:RNA, Messenger