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Originally published In Press as doi:10.1074/mcp.M600393-MCP200 on June 11, 2007.
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Molecular & Cellular Proteomics 6:1680-1689, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Elucidating the Secretion Proteome of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells*,S

Siu Kwan Sze{ddagger}, Dominique P. V. de Kleijn§,¶, Ruenn Chai Lai||, Eileen Khia Way Tan§, Hui Zhao||, Keng Suan Yeo§, Teck Yew Low**, Qizhou Lian§, Chuen Neng Lee{ddagger}{ddagger}, Wayne Mitchell§§, Reida Menshawe El Oakley{ddagger}{ddagger} and Sai-Kiang Lim§,¶¶,||||

From the {ddagger} School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore, § Stem Cell and Developmental Biology, ** Information and Mathematical Sciences, and §§ Proteomics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore, Experimental Cardiology, Utrecht Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands, || Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore, Departments of {ddagger}{ddagger} Surgery and ¶¶ Biochemistry, National University of Singapore, Lower Kent Ridge Road, Singapore 117597, Singapore

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-ß, 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.

|||| To whom correspondence and requests for materials should be addressed: Inst. of Medical Biology, 11 Biopolis St., Helios 02-02, Singapore 138667, Singapore. E-mail: saikiang.lim{at}imboa-star.edu.sg


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