Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells

Siu Kwan Sze, Dominique P V de Kleijn, Ruenn Chai Lai, Eileen Khia Way Tan, Hui Zhao, Keng Suan Yeo, Low Teck Yew, Qizhou Lian, Chuen Neng Lee, Wayne Mitchell, Reida Menshawe El Oakley, Sai Kiang Lim

Research output: Contribution to journalArticle

160 Citations (Scopus)

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 gone 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-β, 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.

Original languageEnglish
Pages (from-to)1680-1689
Number of pages10
JournalMolecular and Cellular Proteomics
Volume6
Issue number10
DOIs
Publication statusPublished - 1 Oct 2007
Externally publishedYes

Fingerprint

Proteome
Stem cells
Mesenchymal Stromal Cells
Hematopoiesis
Conditioned Culture Medium
Tissue
Genes
Mesenchymal Stem Cell Transplantation
Biological Phenomena
Stem Cell Factor
Group Processes
Toll-Like Receptors
Bone Development
Cell Transplantation
Serum-Free Culture Media
Thromboplastin
Transforming Growth Factors
Therapeutic Uses
Repair
Sirolimus

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sze, S. K., de Kleijn, D. P. V., Lai, R. C., Tan, E. K. W., Zhao, H., Yeo, K. S., ... Lim, S. K. (2007). Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Molecular and Cellular Proteomics, 6(10), 1680-1689. https://doi.org/10.1074/mcp.M600393-MCP200

Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. / Sze, Siu Kwan; de Kleijn, Dominique P V; Lai, Ruenn Chai; Tan, Eileen Khia Way; Zhao, Hui; Yeo, Keng Suan; Teck Yew, Low; Lian, Qizhou; Lee, Chuen Neng; Mitchell, Wayne; El Oakley, Reida Menshawe; Lim, Sai Kiang.

In: Molecular and Cellular Proteomics, Vol. 6, No. 10, 01.10.2007, p. 1680-1689.

Research output: Contribution to journalArticle

Sze, SK, de Kleijn, DPV, Lai, RC, Tan, EKW, Zhao, H, Yeo, KS, Teck Yew, L, Lian, Q, Lee, CN, Mitchell, W, El Oakley, RM & Lim, SK 2007, 'Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells', Molecular and Cellular Proteomics, vol. 6, no. 10, pp. 1680-1689. https://doi.org/10.1074/mcp.M600393-MCP200
Sze, Siu Kwan ; de Kleijn, Dominique P V ; Lai, Ruenn Chai ; Tan, Eileen Khia Way ; Zhao, Hui ; Yeo, Keng Suan ; Teck Yew, Low ; Lian, Qizhou ; Lee, Chuen Neng ; Mitchell, Wayne ; El Oakley, Reida Menshawe ; Lim, Sai Kiang. / Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. In: Molecular and Cellular Proteomics. 2007 ; Vol. 6, No. 10. pp. 1680-1689.
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