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Exosomes and Secreted Nano-vesicles

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Sai Kiang Lim

Dr Sai-Kiang Lim graduated with B.Sc (Hons in Biochemistry) from National University of Singapore in 1985. She did her PhD thesis on the metabolism of thalassemic mRNA under Prof Lynne Maquat (Dept. of Human Genetics, Roswell Park Cancer Institute), and was awarded the Most Meritorious Student Research Award by Sigma Xi Society in 1989, NY State Predoctoral Fellowship (1989-91) and a PhD (Molecular Biology) from SUNY at Buffalo in 1992. In 1992, she started postdoctoral training on erythroid differentiation with Prof Frank Constantini (Dept. of Genetics and Development College of Physicians & Surgeons, Columbia University) first as a Cooley’s Anemia Foundation Research Fellow (1992-94) and then a Leukemia Society of America Special Fellow (1994-96).

After postdoctoral training, she led independent research groups at NUMI, NUS (1996-2001), Genome Institute of Singapore (2002-2007) and then Institute of Medical Biology (2007). Her research focus has always been disease-related with emphasis on the elucidation of the underlying molecular and cellular mechanisms in diseases and development of therapies. Her current major research interests are derivation of clinically useful cell types such as mesenchymal stem cells and insulin-producing cell lines from either human or mouse embryonic stem cells and the use of these cells or their products to treat or better understand human diseases.

The current lab was established in 2007 with a research focus on extracellular vesicles (EVs) from stem cells and synthetic EVs for the development of therapeutics, diagnostics, drug delivery systems, nutriceuticals and cosmeticeuticals. 

The lab was the first to demonstrate that mesenchymal stem cells (MSCs) secrete therapeutic exosomes, a class of extracellular vesicles (EVs).  Since then, many of the reported therapeutic efficacies of mesenchymal stem cells for a wide spectrum of diseases were found to be underpinned by EVs.

The major focus of our present research program is to characterize exosomes and other classes of EVs that are secreted by MSCs, and to elucidate the molecular processes for their biogenesis and uptake. We are also investigating several disease indications for MSC exosomes such as acute and chronic myocardial infarction, severe genetic skin diseases e.g. recessive dystrophic epidermolysis bullosa, severe imumune diseases e.g. steroid-refractory graft versus host disease, drug induced liver toxicity. This research has led to the development of several proprietary technological platforms for stem cell or synthetic EV-based therapeutics, diagnostics, drug delivery vehicles, nutriceuticals and cosmeticeuticals.  Since its inception at IMB in 2007, the lab has generated >59 publications, and > 39 granted and 46 pending patents.

The group research program is a highly collaborative, multi-disciplinary endeavour that comprises of local and international basic, clinical and industrial research groups.

 

Group Members

 

Senior Research Fellows Lai Ruenn Chai
  ZHANG Bin
Research Fellow Ronne YEO Wee Yeh
Research Officer TAN Soon Sim
Laboratory Officer Sim Wei Kian

 


RWY Yeo, SK Lim (2016) Exosomes and their Therapeutic Applications. ADVANCES IN PHARMACEUTICAL CELL THERAPY: Principles of Cell-Based Biopharmaceuticals, 477-501 Link
B Zhang, RWY Yeo, KH Tan, SK Lim (2016). Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles International journal of molecular sciences 17 (2), 174 Link
RC Lai, SS Tan, RWY Yeo, ABH Choo, AT Reiner, Y Su, Y Shen, Z Fu, L Alexander, SK Sze, SK Lim (2016). Journal of extracellular vesicles Link
Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes. Semin Cell Dev Biol. 2015 Apr;40:82-8. doi: 10.1016/j.semcdb.2015.03.001. PubMed PMID: 25765629. Link
Tan SS, Chen TS., Tan KH, and Lim SK. (2015). An overview of the proteomic and miRNA cargo in MSC derived exosomes. Chapter 2 pp21-36 in "Mesenchymal Stem Cell Derived Exosomes – The potential for translational nanomedicine. Editors: Yaoliang Tang, Buddhadeb Dawn. Academic Press, 2 Sep 2015. Link
Lener, T., Gioma, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F.A., del Portillo, H.A., et al. (2015). Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. 2015. Journal of Extracellular Vesicles 2015, 4: 30087 Link
Bank, I.E.M., Timmers, L., Gijsberts, C.M., Zhang, Y.-N., Mosterd, A., Wang, J.-W., Chan, M.Y., De Hoog, V., Lim, S.K., Sze, S.K., et al. (2015). The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease. Expert Review of Molecular Diagnostics 15, 1577-1588. Link
Dutta B, Yan R, Lim SK, Tam JP, Sze SK. Quantitative profiling of chromatome dynamics reveals a novel role for HP1BP3 in hypoxia-induced oncogenesis. Mol Cell Proteomics. 2014 Dec;13(12):3236-49. doi: 10.1074/mcp.M114.038232. Epub 2014 Aug 6. PubMed PMID: 25100860; PubMed Central PMCID: PMC4256480. Link
Li X, Ren Y, Sorokin V, Poh KK, Ho HH, Lee CN, de Kleijn D, Lim SK, Tam JP, Sze SK. Quantitative profiling of the rat heart myoblast secretome reveals differential responses to hypoxia and re-oxygenation stress. J Proteomics. 2014 Feb 26;98:138-49. doi: 10.1016/j.jprot.2013.12.025. Epub 2014 Jan 9. PubMed PMID: 24412200. Link
Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther. 2014 Jun 10;5(3):76. doi: 10.1186/scrt465. PubMed PMID: 24915963; PubMed Central PMCID: PMC4229780. Link
Zhang B, Yin Y, Lai RC, Lim SK. Immunotherapeutic potential of extracellular vesicles. Front Immunol. 2014 Oct 22;5:518. doi: 10.3389/fimmu.2014.00518. eCollection 2014. Review. PubMed PMID: 25374570; PubMed Central PMCID: PMC4205852. Link
Zhang B, Yin Y, Lai RC, Tan SS, Choo AB, Lim SK. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2014 Jun 1;23(11):1233-44. doi: 10.1089/scd.2013.0479. Epub 2014 Feb 10. PubMed PMID: 24367916. Link
Tan KH, Tan SS, Sze SK, Lee WK, Ng MJ, Lim SK. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am J Obstet Gynecol. 2014 Oct;211(4):380.e1-13. doi: 10.1016/j.ajog.2014.03.038. Epub 2014 Mar 18. PubMed PMID: 24657793. Link
Tan SS, Yin Y, Lee T, Lai RC, Yeo RW, Zhang B, Choo A, Lim SK. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. J Extracell Vesicles. 2013 Dec 23;2. doi: 10.3402/jev.v2i0.22614. eCollection 2013. PubMed PMID: 24371518; PubMed Central PMCID: PMC3873122. Link
Wang JW, Gijsberts CM, Seneviratna A, de Hoog VC, Vrijenhoek JE, Schoneveld AH, Chan MY, Lam CS, Richards AM, Lee CN, Mosterd A, Sze SK, Timmers L, Lim SK, Pasterkamp G, de Kleijn DP. Plasma extracellular vesicle protein content for diagnosis and prognosis of global cardiovascular disease. Neth Heart J. 2013 Oct;21(10):467-71. doi: 10.1007/s12471-013-0462-3. PubMed PMID: 23975618; PubMed Central PMCID: PMC3776081. Link
Yeo WYR, Lai RC, Tan KH and Lim SK. Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell. Exosomes Microvesicles 2013 1:7. doi: 10.5772/57460. Link
Chen T, Yeo R, Arslan F, Yin Y, Tan SS, Choo A, Padmanabhand J, Lee CN, de Kleijn DPV, Tan KH and Lim SK. Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor. 2013 J Stem Cell Res Ther 3, 2. Link
Ren Y, Hao P, Dutta B, Cheow ES, Sim KH, Gan CS, Lim SK, Sze SK. Hypoxia modulates A431 cellular pathways association to tumor radioresistance and enhanced migration revealed by comprehensive proteomic and functional studies. Mol Cell Proteomics. 2013 Feb;12(2):485-98. doi: 10.1074/mcp.M112.018325. Epub 2012 Nov 30. PubMed PMID: 23204318; PubMed Central PMCID: PMC3567868. Link
Chen TS, Lim SK. Measurement of precursor miRNA in exosomes from human ESC-derived mesenchymal stem cells. Methods Mol Biol. 2013;1024:69-86. doi: 10.1007/978-1-62703-453-1_6. PubMed PMID: 23719943. Link
Lai RC, Yeo RW, Tan KH, Lim SK. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv. 2013 Sep-Oct;31(5):543-51. doi: 10.1016/j.biotechadv.2012.08.008. Epub 2012 Aug 25. Review. PubMed PMID: 22959595. Link
Lai RC, Yeo RW, Tan KH, Lim SK. Mesenchymal stem cell exosome ameliorates reperfusion injury through proteomic complementation. Regen Med. 2013 Mar;8(2):197-209. doi: 10.2217/rme.13.4. Review. PubMed PMID: 23477399. Link
Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev. 2013 Mar;65(3):336-41. doi: 10.1016/j.addr.2012.07.001. Epub 2012 Jul 7. Review. PubMed PMID: 22780955 Link
Kanhai DA, Visseren FL, van der Graaf Y, Schoneveld AH, Catanzariti LM, Timmers L, Kappelle LJ, Uiterwaal CS, Lim SK, Sze SK, Pasterkamp G, de Kleijn DP; SMART Study Group. Microvesicle protein levels are associated with increased risk for future vascular events and mortality in patients with clinically manifest vascular disease. Int J Cardiol. 2013 Oct 3;168(3):2358-63. doi: 10.1016/j.ijcard.2013.01.231. Epub 2013 Feb 26. PubMed PMID: 23484740. Link
Lai R, Yeo R, Tan S, Zhang B, Yin Y, Sze S, Choo A, and Lim S. Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy? 2013. In Mesenchymal Stem Cell Therapy, L.G.V. Chase, Mohan C. , ed. (Humana Press), pp. 39-62. ISBN 978-1-62703-200-1
Arslan F, Smeets MB, Buttari B, Profumo E, Riganò R, Akeroyd L, Kara E, Timmers L, Sluijter JP, van Middelaar B, den Ouden K, Pasterkamp G, Lim SK, de Kleijn DP. Lack of haptoglobin results in unbalanced VEGFα/angiopoietin-1 expression, intramural hemorrhage and impaired wound healing after myocardial infarction. J Mol Cell Cardiol. 2013 Mar;56:116-28. doi: 10.1016/j.yjmcc.2012.12.012. Epub 2012 Dec 26. PubMed PMID: 23274064. Link
Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, Timmers L, van Rijen HV, Doevendans PA, Pasterkamp G, Lim SK, de Kleijn DP. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 2013 May;10(3):301-12. doi: 10.1016/j.scr.2013.01.002. Epub 2013 Jan 14. PubMed PMID: 23399448. Link
Tan KH, Lim SK. Extracellular Vesicles–A New Frontier In Medical Research. Researchers Can Tap On This Area For Opportunities To Further Improve Clinical Care. 2012 The Internet Journal of Gynecology and Obstetrics 16(3) DOI: 10.5580/2bf1. Link
Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, Bond VC, Borràs FE, Breakefield X, Budnik V, Buzas E, Camussi G, Clayton A, Cocucci E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers EM, Lim SK, Llorente A, Lötvall J, Marcilla A, Mincheva-Nilsson L, Nazarenko I, Nieuwland R, Nolte-'t Hoen EN, Pandey A, Patel T, Piper MG, Pluchino S, Prasad TS, Rajendran L, Raposo G, Record M, Reid GE, Sánchez-Madrid F, Schiffelers RM, Siljander P, Stensballe A, Stoorvogel W, Taylor D, Thery C, Valadi H, van Balkom BW, Vázquez J, Vidal M, Wauben MH, Yáñez-Mó M, Zoeller M, Mathivanan S. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):e1001450. doi: 10.1371/journal.pbio.1001450. Epub 2012 Dec 18. PubMed PMID: 23271954; PubMed Central PMCID: PMC3525526. Link
Dutta B, Adav SS, Koh CG, Lim SK, Meshorer E, Sze SK. Elucidating the temporal dynamics of chromatin-associated protein release upon DNA digestion by quantitative proteomic approach. J Proteomics. 2012 Sep 18;75(17):5493-506. doi: 10.1016/j.jprot.2012.06.030. Epub 2012 Jul 13. PubMed PMID: 22796351. Link
Chu PP, Bari S, Fan X, Gay FP, Ang JM, Chiu GN, Lim SK, Hwang WY. Intercellular cytosolic transfer correlates with mesenchymal stromal cell rescue of umbilical cord blood cell viability during ex vivo expansion. Cytotherapy. 2012 Oct;14(9):1064-79. doi: 10.3109/14653249.2012.697146. Epub 2012 Jul 10. PubMed PMID: 22775077; PubMed Central PMCID: PMC3484967. Link
van Koppen A, Joles JA, van Balkom BW, Lim SK, de Kleijn D, Giles RH, Verhaar MC. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease. PLoS One. 2012;7(6):e38746. doi: 10.1371/journal.pone.0038746. Epub 2012 Jun 19. PubMed PMID: 22723882; PubMed Central PMCID: PMC3378606 Link
Ong LM, Fan X, Chu PP, Gay FP, Bari S, Ang JM, Li Z, Chen J, Lim SK, Bunte RM, Hwang WY. Cotransplantation of ex vivo expanded and unexpanded cord blood units in immunodeficient mice using insulin growth factor binding protein-2-augmented mesenchymal cell cocultures. Biol Blood Marrow Transplant. 2012 May;18(5):674-82. doi: 10.1016/j.bbmt.2012.01.001. Epub 2012 Jan 9. PubMed PMID: 22240732. Link
Lai RC, Tan SS, Teh BJ, Sze SK, Arslan F, de Kleijn DP, Choo A, Lim SK. Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome. Int J Proteomics. 2012;2012:971907. doi: 10.1155/2012/971907. Epub 2012 Jul 18. PubMed PMID: 22852084; PubMed Central PMCID: PMC3407643. Link
Yeo RW, Yang K, Li G, Lim SK. High glucose predisposes gene expression and ERK phosphorylation to apoptosis and impaired glucose-stimulated insulin secretion via the cytoskeleton. PLoS One. 2012;7(9):e44988. Epub 2012 Sep 14. PubMed PMID: 23024780; PubMed Central PMCID: PMC3443235. Link
Li X, Arslan F, Ren Y, Adav SS, Poh KK, Sorokin V, Lee CN, de Kleijn D, Lim SK, Sze SK. Metabolic adaptation to a disruption in oxygen supply during myocardial ischemia and reperfusion is underpinned by temporal and quantitative changes in the cardiac proteome. J Proteome Res. 2012 Apr 6;11(4):2331-46. doi: 10.1021/pr201025m. Epub 2012 Mar 8. PubMed PMID: 22352837. Link
Yeo WYR, Lim SK. Embryonic Stem Cells for Therapies – Challenges and Possibilities, Embryonic Stem Cells - Basic Biology to Bioengineering, Prof. Michael Kallos (Ed.), 2011 ISBN: 978-953-307-278-4, InTech, DOI: 10.5772/23762.
Lai RC, Choo A, Lim SK. Derivation and characterization of human ESC-derived mesenchymal stem cells. Methods Mol Biol. 2011;698:141-50. doi: 10.1007/978-1-60761-999-4_11. PubMed PMID: 21431516. Link
Choo A, Lim SK. Derivation of mesenchymal stem cells from human embryonic stem cells. Methods Mol Biol. 2011;690:175-82. doi: 10.1007/978-1-60761-962-8_12. PubMed PMID: 21042993. Link
Bak XY, Lam DH, Yang J, Ye K, Wei EL, Lim SK, Wang S. Human embryonic stem cell-derived mesenchymal stem cells as cellular delivery vehicles for prodrug gene therapy of glioblastoma. Hum Gene Ther. 2011 Nov;22(11):1365-77. doi: 10.1089/hum.2010.212. Epub 2011 May 16. PubMed PMID: 21425958. Link
Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med. 2011 Jul;6(4):481-92. doi: 10.2217/rme.11.35. Review. PubMed PMID: 21749206. Link
Chen TS, Arslan F, Yin Y, Tan SS, Lai RC, Choo AB, Padmanabhan J, Lee CN, de Kleijn DP, Lim SK. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med. 2011 Apr 25;9:47. doi: 10.1186/1479-5876-9-47. PubMed PMID: 21513579; PubMed Central PMCID: PMC3100248. Link
Timmers L, Lim SK, Hoefer IE, Arslan F, Lai RC, van Oorschot AA, Goumans MJ, Strijder C, Sze SK, Choo A, Piek JJ, Doevendans PA, Pasterkamp G, de Kleijn DP. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 2011 May;6(3):206-14. doi: 10.1016/j.scr.2011.01.001. Epub 2011 Jan 28. PubMed PMID: 21419744. Link
Shao S, Gao Y, Xie B, Xie F, Lim SK, Li G. Correction of hyperglycemia in type 1 diabetic models by transplantation of encapsulated insulin-producing cells derived from mouse embryo progenitor. J Endocrinol. 2011 Mar;208(3):245-55. doi: 10.1530/JOE-10-0378. Epub 2011 Jan 6. PubMed PMID: 21212095. Link
Chen TS, Tan SS, Yeo RW, Teh BJ, Luo R, Li G, Lim SK. Delineating biological pathways unique to embryonic stem cell-derived insulin-producing cell lines from their noninsulin-producing progenitor cell lines. Endocrinology. 2010 Aug;151(8):3600-10. doi: 10.1210/en.2009-1418. Epub 2010 May 25. PubMed PMID: 20501672. Link
Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK. Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics. 2010 Jun;9(6):1085-99. doi: 10.1074/mcp.M900381-MCP200. Epub 2010 Feb 1. PubMed PMID: 20124223; PubMed Central PMCID: PMC2877972. Link
Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4. PubMed PMID: 20138817. Link
Lai RC, Arslan F, Tan SS, Tan B, Choo A, Lee MM, Chen TS, Teh BJ, Eng JK, Sidik H, Tanavde V, Hwang WS, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Tan KH, Lim SK. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles. J Mol Cell Cardiol. 2010 Jun;48(6):1215-24. doi: 10.1016/j.yjmcc.2009.12.021. Epub 2010 Jan 11. PubMed PMID: 20064522. Link
Zhang H, Guo T, Li X, Datta A, Park JE, Yang J, Lim SK, Tam JP, Sze SK. Simultaneous characterization of glyco- and phosphoproteomes of mouse brain membrane proteome with electrostatic repulsion hydrophilic interaction chromatography. Mol Cell Proteomics. 2010 Apr;9(4):635-47. doi: 10.1074/mcp.M900314-MCP200. Epub 2010 Jan 4. PubMed PMID: 20047950; PubMed Central PMCID: PMC2860239. Link
de Kleijn DP, Moll FL, Hellings WE, Ozsarlak-Sozer G, de Bruin P, Doevendans PA, Vink A, Catanzariti LM, Schoneveld AH, Algra A, Daemen MJ, Biessen EA, de Jager W, Zhang H, de Vries JP, Falk E, Lim SK, van der Spek PJ, Sze SK, Pasterkamp G. Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events. Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):612-9. doi: 10.1161/ATVBAHA.109.194944. Epub 2009 Dec 17. PubMed PMID: 20018935. Link
Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS, Tanavde V. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics. 2010 Feb 10;11 Suppl 1:S6. doi: 10.1186/1471-2164-11-S1-S6. PubMed PMID: 20158877; PubMed Central PMCID: PMC2822534. Link
Chen TS, Lai RC, Lee MM, Choo AB, Lee CN, Lim SK. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 2010 Jan;38(1):215-24. doi: 10.1093/nar/gkp857. Epub 2009 Oct 22. PubMed PMID: 19850715; PubMed Central PMCID: PMC2800221. Link
Datta A, Park JE, Li X, Zhang H, Ho ZS, Heese K, Lim SK, Tam JP, Sze SK. Phenotyping of an in vitro model of ischemic penumbra by iTRAQ-based shotgun quantitative proteomics. J Proteome Res. 2010 Jan;9(1):472-84. doi: 10.1021/pr900829h. PubMed PMID: 19916522. Link
Li G, Luo R, Zhang J, Yeo KS, Lian Q, Xie F, Tan EK, Caille D, Kon OL, Salto-Tellez M, Meda P, Lim SK. Generating mESC-derived insulin-producing cell lines through an intermediate lineage-restricted progenitor line. Stem Cell Res. 2009 Jan;2(1):41-55. doi: 10.1016/j.scr.2008.07.006. Epub 2008 Aug 8. PubMed PMID: 19383408. Link
Li G, Luo R, Zhang J, Yeo KS, Xie F, Way Tan EK, Caille D, Que J, Kon OL, Salto-Tellez M, Meda P, Lim SK. Derivation of functional insulin-producing cell lines from primary mouse embryo culture. Stem Cell Res. 2009 Jan;2(1):29-40. doi:10.1016/j.scr.2008.07.004. Epub 2008 Jul 31. PubMed PMID: 19383407. Link
van Keulen JK, Timmers L, van Kuijk LP, Retnam L, Hoefer IE, Pasterkamp G, Lim SK, de Kleijn DP. The Nuclear Factor-kappa B p50 subunit is involved in flow-induced outward arterial remodeling. Atherosclerosis. 2009 Feb;202(2):424-30. doi: 10.1016/j.atherosclerosis.2008.05.049. Epub 2008 Jun 5. PubMed PMID: 18617174. Link
Zhu Y, Guo T, Park JE, Li X, Meng W, Datta A, Bern M, Lim SK, Sze SK. Elucidating in vivo structural dynamics in integral membrane protein by hydroxyl radical footprinting. Mol Cell Proteomics. 2009 Aug;8(8):1999-2010. doi: 10.1074/mcp.M900081-MCP200. Epub 2009 May 26. PubMed PMID: 19473960; PubMed Central PMCID: PMC2722762. Link
van Oostrom O, de Kleijn DP, Fledderus JO, Pescatori M, Stubbs A, Tuinenburg A, Lim SK, Verhaar MC. Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study. Cardiovasc Diabetol. 2009 Aug 25;8:47. doi: 10.1186/1475-2840-8-47. PubMed PMID: 19706161; PubMed Central PMCID: PMC2739843. Link
Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley RM, Choo A, Lee CN, Pasterkamp G, de Kleijn DP. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res. 2007 Nov;1(2):129-37. doi: 10.1016/j.scr.2008.02.002. Epub 2008 Mar 8. PubMed PMID: 19383393. Link
Choo A, Ngo AS, Ding V, Oh S, Kiang LS. Autogeneic feeders for the culture of undifferentiated human embryonic stem cells in feeder and feeder-free conditions. Methods Cell Biol. 2008;86:15-28. doi: 10.1016/S0091-679X(08)00002-2. PubMed PMID: 18442642. Link
Chee SG, Guo T, Zhang H, Lim SK, Sze SK. A comparative study of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) versus SCX-IMAC-based methods for phosphopeptide isolation/enrichment. J Proteome Res. 2008 Nov;7(11):4869-77. doi: 10.1021/pr800473j. Epub 2008 Oct 2. PubMed PMID: 18828627. Link
Lian Q, Lye E, Suan Yeo K, Khia Way Tan E, Salto-Tellez M, Liu TM, Palanisamy N, El Oakley RM, Lee EH, Lim B, Lim SK. Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs. Stem Cells. 2007 Feb;25(2):425-36. Epub 2006 Oct 19. PubMed PMID: 17053208. Link
Sze SK, de Kleijn DP, Lai RC, Khia Way Tan E, Zhao H, Yeo KS, Low TY, Lian Q, Lee CN, Mitchell W, El Oakley RM, Lim SK. Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Mol Cell Proteomics.2007 Oct;6(10):1680-9. Epub 2007 Jun 11. PubMed PMID: 17565974. Link
Que J, Lian Q, El Oakley RM, Lim B, Lim SK. PI3 K/Akt/mTOR-mediated translational control regulates proliferation and differentiation of lineage-restricted RoSH stem cell lines. J Mol Signal. 2007 Sep 25;2:9. PubMed PMID: 17892597; PubMed Central PMCID: PMC2045085. Link