Basic research


A report on the International Society for Cell & Gene Therapy 2022 Scientific Signature Series, “Therapeutic advances with native and engineered human extracellular vesicles” (Toh, W. S., Yarani, R., El Andaloussi, S., Cho, B. S., Choi, C., Corteling, R., De Fougerolles, A., Gimona, M., Herz, J., Khoury, M., Robbins, P. D., Williams, D., Weiss, D. J., Rohde, E., Giebel, B., & Lim, S. K.) (2023). Cytotherapy, 25(8), 810–814. Link


Extracellular Vesicles and Their Emerging Roles as Cellular Messengers in Endocrinology: An Endocrine Society Scientific Statement (Salomon, C., Das, S., Erdbrügger, U., Kalluri, R., Kiang Lim, S., Olefsky, J. M., Rice, G. E., Sahoo, S., Andy Tao, W., Vader, P., Wang, Q., & Weaver, A. M.) (2022). Endocrine reviews, 43(3), 441–468. Link


Assessment of Tumorigenic Potential in Mesenchymal-Stem/Stromal-Cell-Derived Small Extracellular Vesicles (MSC-sEV) (Tan, T. T., Lai, R. C., Padmanabhan, J., Sim, W. K., Choo, A. B. H., & Lim, S. K.) (2021). Pharmaceuticals (Basel, Switzerland), 14(4), 345. Link

Practical considerations in transforming MSC therapy for neurological diseases from cell to EV (Tan, T. T., Toh, W. S., Lai, R. C., & Lim, S. K.) (2022). Experimental neurology, 349, 113953. Link

Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles (Gimona, M., Brizzi, M. F., Choo, A. B. H., Dominici, M., Davidson, S. M., Grillari, J., Hermann, D. M., Hill, A. F., de Kleijn, D., Lai, R. C., Lai, C. P., Lim, R., Monguió-Tortajada, M., Muraca, M., Ochiya, T., Ortiz, L. A., Toh, W. S., Yi, Y. W., Witwer, K. W., Giebel, B., … Lim, S. K.) (2021). Cytotherapy, 23(5), 373–380. Link


Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications (Witwer, K. W., Van Balkom, B. W. M., Bruno, S., Choo, A., Dominici, M., Gimona, M., Hill, A. F., De Kleijn, D., Koh, M., Lai, R. C., Mitsialis, S. A., Ortiz, L. A., Rohde, E., Asada, T., Toh, W. S., Weiss, D. J., Zheng, L., Giebel, B., & Lim, S. K.) (2019). Journal of extracellular vesicles, 8(1), 1609206. Link

A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma (Rodrigues-Junior, D. M., Tan, S. S., de Souza Viana, L., Carvalho, A. L., Lim, S. K., Iyer, N. G., & Vettore, A. L.) (2019). BMC cancer, 19(1), 373. Link

Circulating extracellular vesicle-associated TGFβ3 modulates response to cytotoxic therapy in head and neck squamous cell carcinoma (Rodrigues-Junior, D. M., Tan, S. S., Lim, S. K., Leong, H. S., Melendez, M. E., Ramos, C. R. N., Viana, L. S., Tan, D. S. W., Carvalho, A. L., Iyer, N. G., & Vettore, A. L.) (2019). Carcinogenesis, 40(12), 1452–1461. Link

Membrane lipid binding molecules for the isolation of bona fide extracellular vesicle types and associated biomarkers in liquid biopsy (Lai, R. C., Tan, K. H., & Lim, S. K.) (2019). Journal of Cancer Metastasis and Treatment, 5(65). Link


Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. (Théry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., … Zuba-Surma, E. K.) (2018). Journal of extracellular vesicles, 7(1), 1535750. Link

Proteomic Signature of Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles. (van Balkom, B. W. M., Gremmels, H., Giebel, B., & Lim, S. K.) (2019). Proteomics, 19(1-2), e1800163. Link

High expression of MLANA in the plasma of patients with head and neck squamous cell carcinoma as a predictor of tumor progression. (Rodrigues-Junior, D. M., Tan, S. S., Lim, S. K., de Souza Viana, L., Carvalho, A. L., Vettore, A. L., & Iyer, N. G.) (2019). Head & neck, 41(5), 1199–1205. Link

Membrane lipids define small extracellular vesicle subtypes secreted by mesenchymal stromal cells. (Lai, R. C., & Lim, S. K.) (2019). Journal of lipid research, 60(2), 318–322. Link

MSC exosome works through a protein-based mechanism of action. (Toh, W. S., Lai, R. C., Zhang, B., & Lim, S. K.) (2018). Biochemical Society transactions, 46(4), 843–853. Link


Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles. (Reiner, A. T., Witwer, K. W., van Balkom, B. W. M., de Beer, J., Brodie, C., Corteling, R. L., Gabrielsson, S., Gimona, M., Ibrahim, A. G., de Kleijn, D., Lai, C. P., Lötvall, J., Del Portillo, H. A., Reischl, I. G., Riazifar, M., Salomon, C., Tahara, H., Toh, W. S., Wauben, M. H. M., Yang, V. K., … Lim, S. K.) (2017). Stem cells translational medicine, 6(8), 1730–1739. Link

Dietary phytochemical PEITC restricts tumor development via modulation of epigenetic writers and erasers. (Park, J. E., Sun, Y., Lim, S. K., Tam, J. P., Dekker, M., Chen, H., & Sze, S. K.) (2017). Scientific reports, 7, 40569. Link

EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs. (Reiner, A. T., Tan, S., Agreiter, C., Auer, K., Bachmayr-Heyda, A., Aust, S., Pecha, N., Mandorfer, M., Pils, D., Brisson, A. R., Zeillinger, R., & Lim, S. K.) (2017). Disease markers, 2017, 9653194. Link

Extracellular vesicles yield predictive pre-eclampsia biomarkers. (Tan, K. H., Tan, S. S., Ng, M. J., Tey, W. S., Sim, W. K., Allen, J. C., & Lim, S. K.) (2017). Journal of extracellular vesicles, 6(1), 1408390. Link

Magnetic nanoparticle-enhanced surface plasmon resonance biosensor for extracellular vesicle analysis. (Reiner, A. T., Ferrer-Sanchez, N. G., Venugopalan, P., Lai, R. C., Lim, S. K., & Dostálek, J.) (2017, August 24). The Analyst, 142. Link


Isolation and Characterization of Exosome from Human Embryonic Stem Cell-Derived C-Myc-Immortalized Mesenchymal Stem Cells. (Lai, R. C., Yeo, R. W., Padmanabhan, J., Choo, A., de Kleijn, D. P., & Lim, S. K.) (2016). Methods in molecular biology (Clifton, N.J.), 1416, 477–494. Link

MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. (Lai, R. C., Tan, S. S., Yeo, R. W., Choo, A. B., Reiner, A. T., Su, Y., Shen, Y., Fu, Z., Alexander, L., Sze, S. K., & Lim, S. K.) (2016). Journal of extracellular vesicles, 5, 29828. Link

Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. (Zhang, B., Yeo, R. W., Tan, K. H., & Lim, S. K.) (2016). International journal of molecular sciences, 17(2), 174. Link


Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. (Lener, T., Gimona, M., Aigner, L., Börger, V., Buzas, E., Camussi, G., Chaput, N., Chatterjee, D., Court, F. A., Del Portillo, H. A., O’Driscoll, L., Fais, S., Falcon-Perez, J. M., Felderhoff-Mueser, U., Fraile, L., Gho, Y. S., Görgens, A., Gupta, R. C., Hendrix, A., Hermann, D. M., … Giebel, B.) (2015). Journal of extracellular vesicles, 4, 30087. Link

Mesenchymal stem cell exosomes. (Lai, R. C., Yeo, R. W., & Lim, S. K.) (2015). Seminars in cell & developmental biology, 40, 82–88. Link


Immunotherapeutic Potential of Extracellular Vesicles. (Zhang, B., Yin, Y., Lai, R.C., & Lim, S.K.) (2014). Frontiers in Immunology, 5. Link

Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. (Tan, K. H., Tan, S. S., Sze, S. K., Lee, W. K., Ng, M. J., & Lim, S. K.) (2014). American journal of obstetrics and gynecology, 211(4), 380.e1–380.e3813. Link


Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor. (Chen, T. S., Yeo, R. W. Y., Arslan, F., Yin, Y., Tan, S. S., Lai, R. C., Choo, A., Padmanabhan, J., Lee, C. N., de Kleijn, D. P. V., Tan, K. H., & Lim, S. K.) (2013). Journal of Stem Cell Research & Therapy, 3(3). Link

Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell. (Yeo, R. W. Y., Lai, R. C., Tan, K. H., & Lim, S. K.) (2013). Exosomes and Microvesicles, 1(7). Link

Measurement of precursor miRNA in exosomes from human ESC-derived mesenchymal stem cells. (Chen, T. S., & Lim, S. K.) (2013). Methods in molecular biology (Clifton, N.J.)1024, 69–86. Link

Mesenchymal stem cell exosomes: The future MSC-based therapy? (Lai, R. C., Yeo, R., Tan, S. S., Zhang, B., Yin, Y., Sze, N. S. K., Choo, A., & Lim, S. K.) (2013). Mesenchymal Stem Cell Therapy, 1(pages 39-62). Link

Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. (Tan, S. S., Yin, Y., Lee, T., Lai, R. C., Yeo, R. W., Zhang, B., Choo, A., & Lim, S. K.) (2013). Journal of extracellular vesicles, 2. Link


Embryonic Stem Cells for Therapies – Challenges and Possibilities. (Yeh Yeo, R. W., & Kiang, S.) (2012). InTech. Link

Metabolic adaptation to a disruption in oxygen supply during myocardial ischemia and reperfusion is underpinned by temporal and quantitative changes in the cardiac proteome. (Li, X., Arslan, F., Ren, Y., Adav, S. S., Poh, K. K., Sorokin, V., Lee, C. N., de Kleijn, D., Lim, S. K., & Sze, S. K.) (2012). Journal of proteome research, 11(4), 2331–2346. Link

Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome. (Lai, R. C., Tan, S. S., Teh, B. J., Sze, S. K., Arslan, F., de Kleijn, D. P., Choo, A., & Lim, S. K.) (2012). International journal of proteomics, 2012, 971907. Link


Derivation and Characterization of Human ESC-Derived Mesenchymal Stem Cells. (Lai, R. C., Choo, A., & Lim, S. K.) (2011). Methods in molecular biology (Clifton, N.J.), 698, 141–150. Link

Enabling a Robust Scalable Manufacturing Process for Therapeutic Exosomes Through Oncogenic Immortalization of Human ESC-Derived MSCs. (Chen, T. S., Arslan, F., Yin, Y., Tan, S. S., Lai, R. C., Choo, A. B., Padmanabhan, J., Lee, C. N., de Kleijn, D. P., & Lim, S. K.) (2011). Journal of translational medicine, 9, 47. Link


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. (Koh, W., Sheng, C. T., Tan, B., Lee, Q. Y., Kuznetsov, V., Kiang, L. S., & Tanavde, V.) (2010). BMC genomics, 11 Suppl 1(Suppl 1), S6. Link

Derivation and Characterization of Human Fetal MSCs: An Alternative Cell Source for Large-Scale Production of Cardioprotective Microparticles. (Lai, R. C., Arslan, F., Tan, S. S., Tan, B., Choo, A., Lee, M. M., Chen, T. S., Teh, B. J., Eng, J. K., Sidik, H., Tanavde, V., Hwang, W. S., Lee, C. N., El Oakley, R. M., Pasterkamp, G., de Kleijn, D. P., Tan, K. H., & Lim, S. K.) (2010). Journal of Molecular and Cellular Cardiology, 48(6), 1215–1224. Link

Hypoxic Tumor Cell Modulates Its Microenvironment to Enhance Angiogenic and Metastatic Potential by Secretion of Proteins and Exosomes. (Park, J. E., Tan, H. S., Datta, A., Lai, R. C., Zhang, H., Meng, W., Lim, S. K., & Sze, S. K.) (2010). Molecular & Cellular Proteomics: MCP, 9(6), 1085–1099. Link

Local Atherosclerotic Plaques Are a Source of Prognostic Biomarkers for Adverse Cardiovascular Events. (de Kleijn, D. P., Moll, F. L., Hellings, W. E., Ozsarlak-Sozer, G., de Bruin, P., Doevendans, P. A., Vink, A., Catanzariti, L. M., Schoneveld, A. H., Algra, A., Daemen, M. J., Biessen, E. A., de Jager, W., Zhang, H., de Vries, J. P., Falk, E., Lim, S. K., van der Spek, P. J., Sze, S. K., & Pasterkamp, G.) (2010). Arteriosclerosis, Thrombosis, and Vascular Biology, 30(3), 612–619. Link

Mesenchymal Stem Cell Secretes Microparticles Enriched in Pre-microRNAs. (Chen, T. S., Lai, R. C., Lee, M. M., Choo, A. B., Lee, C. N., & Lim, S. K.) (2010). Nucleic Acids Research, 38(1), 215–224. Link


Elucidating In Vivo Structural Dynamics in Integral Membrane Protein by Hydroxyl Radical Footprinting. (Zhu, Y., Guo, T., Park, J. E., Li, X., Meng, W., Datta, A., Bern, M., Lim, S. K., & Sze, S. K.) (2009). Molecular & Cellular Proteomics, 8(8), 1999–2010. Link

Folic Acid Supplementation Normalizes the Endothelial Progenitor Cell Transcriptome of Patients with Type 1 Diabetes: A Case-Control Pilot Study. (van Oostrom, O., de Kleijn, D. P., Fledderus, J. O., Pescatori, M., Stubbs, A., Tuinenburg, A., Lim, S. K., & Verhaar, M. C.) (2009). Cardiovascular Diabetology, 8, 47. Link

The Nuclear Factor-kappa B p50 Subunit Is Involved in Flow-Induced Outward Arterial Remodeling. (van Keulen, J. K., Timmers, L., van Kuijk, L. P., Retnam, L., Hoefer, I. E., Pasterkamp, G., Lim, S. K., & de Kleijn, D. P.) (2009). Atherosclerosis, 202(2), 424–430. Link


A Comparative Study of Electrostatic Repulsion-Hydrophilic Interaction Chromatography (ERLIC) versus SCX-IMAC-Based Methods for Phosphopeptide Isolation/Enrichment. (Gan, C. S., Guo, T., Zhang, H., Lim, S. K., & Sze, S. K.) (2008). Journal of Proteome Research, 7(11), 4869–4877. Link


Derivation of Clinically Compliant MSCs from CD105+, CD24- Differentiated Human ESCs. (Lian, Q., Lye, E., Suan Yeo, K., Khia Way Tan, E., Salto-Tellez, M., Liu, T. M., Palanisamy, N., El Oakley, R. M., Lee, E. H., Lim, B., & Lim, S. K.) (2007). Stem Cells (Dayton, Ohio), 25(2), 425–436. Link

Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. (Sze, S. K., de Kleijn, D. P., Lai, R. C., Khia Way Tan, E., Zhao, H., Yeo, K. S., Low, T. Y., Lian, Q., Lee, C. N., Mitchell, W., El Oakley, R. M., & Lim, S. K.) (2007). Molecular & cellular proteomics : MCP, 6(10), 1680–1689. Link


Mast cell-derived exosomes activate endothelial cells to secrete plasminogen activator inhibitor type 1. (Al-Nedawi, K., Szemraj, J., & Cierniewski, C. S.) (2005). Arteriosclerosis, thrombosis, and vascular biology, 25(8), 1744–1749. Link


Myocardial infarction in the C57BL/6J mouse: a quantifiable and highly reproducible experimental model. (Salto-Tellez, M., Yung Lim, S., El-Oakley, R. M., Tang, T. P., ALmsherqi, Z. A., & Lim, S. K.) (2004). Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology, 13(2), 91–97. Link


AFP(+), ESC-derived cells engraft and differentiate into hepatocytes in vivo. (Yin, Y., Lim, Y. K., Salto-Tellez, M., Ng, S. C., Lin, C. S., & Lim, S. K.) (2002). Stem cells (Dayton, Ohio), 20(4), 338–346. Link

Gonadal effects on plasma ACE activity in mice. (Lim, Y. K., Retnam, L., Bhagavath, B., Sethi, S. K., bin Ali, A., & Lim, S. K.) (2002). Atherosclerosis, 160(2), 311–316. Link

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