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Engineering CELLS,
   Engineering RESPONSES

Stem Cells

Seek to Cure

The Stem Cell Group is focused on the discovery of novel monoclonal antibodies (mAbs) and elucidating key signaling pathways regulating stem cell fates. Notably, results obtained from in vitro studies have shown that these mAbs specifically bind and kill cancer cells of the breast, ovarian, kidney, colorectal and liver tumour types. At present, we are evaluating these candidate mAbs for their in vivo efficacy in tumour xenograft models. Besides therapeutic applications, our mAbs hold potential in cell therapy, disease diagnostics and in vivo imaging.

We have also established an Antibody Discovery Platform (ADP) which facilitates the generation of novel cytotoxic mAbs toward cell surface markers on stem cells and cancer cells. This leveraged on the expertise previously developed for a panel of cytotoxic monoclonal antibodies (mAbs) toward human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) for the purpose of eliminating residual teratoma-forming PSCs after differentiation.

Keeping in mind that an antibody is useful in research and industry when it can be efficiently produced in large quantities, other capabilities within BTI, such as the Animal Cell Technology (ACT) and Downstream Processing (DP) groups, have proven invaluable in aiding us with several technologies which include cell enrichment and bioprocessing of our mAbs. Furthermore, characterization of antigen targets is achieved with a variety of proteomics and glycomics tools, and expertise provided by the Analytics group.

The overarching goal of our studies is thus two-fold: to develop and characterize novel cytotoxic mAbs which recognize surface antigens for eliminating stem cells and cancer cells in the clinical setting, and to elucidate stem cell regulation as well as disease biology at the molecular level. We are hopeful that our active ongoing collaborations with fellow academics, clinicians, as well as several industry players, would enable the smooth transition of these mAbs toward future clinical applications.

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Today’s Research, Tomorrow’s Cellular Therapy

The Stem Cells 2 Group is focused on developing scalable cell expansion technologies using a microcarrier platform to facilitate the goal of using stem cells for cell therapy. Traditional methods of producing anchorage dependent stem cells in flasks and trays are not scalable for commercial cell production. Therefore new methods of stem cell production in bioreactors are urgently needed.

To achieve the goal of producing stem cells in quantities required for therapeutic applications, we have developed expertise in suspension bioreactor cultures using a variety of microcarriers to expand stem cells (human embryonic, pluripotent, and mesenchymal stem cells) to densities 3 to 10 fold higher than conventional 2D cultures. We have experience in culturing these stem cells in serum free media and defined surfaces. High yields of cardiomyocytes, neural stem cells and osteoblasts have also been established on this platform.

Non-invasive bioprocess monitoring of pluripotent stem cells and cardiomyocytes are also being developed with SIMTech and I2R. In addition, we are developing biodegradable microcarriers together with collaborations at IMRE, with dual purposes for cell culture and implantation in vivo; and small molecules for differentiating stem cells to cardiomyocytes (with ICES), neural progenitors and osteocytes.

Furthermore we are working with clinical partners (NUHS and Hong Kong University) to deliver stem cells to animal models of heart, bone, and cartilage repair.

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People

Dr. Steve Oh

PhD in Chemical Engineering (1991), University of Birmingham, UK

Research Focus/Interests
  • Microcarrier cultures of pluripotent stem cells
  • Bioreactor expansion of fetal MSC and hESC
  • Engineered surfaces for hESC cultures
  • Differentiation of hESC derived cardiomyocytes with small molecule inhibitors
  • Imaging/monitoring of pluripotent stem cells and cardiomyocytes

Dr. Andre Choo

PhD in Biological Science (2002), University of Technology, Sydney, Australia

Research Focus/Interests
  • Generation and characterization of novel anti-glycan mAbs to cell surface markers on stem cells, progenitor cells and cancer cells
  • Development of a comprehensive Antibody Discovery Platform to move candidate mAbs from the bench to potential diagnostic and therapeutic applications
  • Unravel the underlying mechanism of oncotic cell killing by mAbs
  • Elucidating key signalling pathway and post-translation modifications in pluripotent stem cells and cancer cells and understanding its role in regulating cell fate
  • Translating the therapeutic efficacy of MSC exosomes into a clinical application

Dr. Vanessa Ding

PhD in Stem Cell Biology (2010), National University of Singapore, Singapore

Research Focus/Interests
  • Signaling mechanisms in undifferentiated human embryonic stem cells
  • Global phosphoproteome profiling in human embryonic stem cell
  • Generation and characterization of novel monoclonal antibodies to cell surface markers (Antibody Discovery Platform)

Dr. Alan Lam

PhD in Biochemistry (2003), Chinese University of Hong Kong, Hong Kong

Research Focus/Interests
  • Engineering a scalable 3D microcarrier-based technology for hESC-derived cardiomyocytes

Dr. Melissa Lin

PhD in Human Biology and Translational Medicine (2014), Harvard Medical School, Harvard University, USA

Research Focus/Interests
  • Scalable, biodegradable and bioimplantable microcarrier-based technologies for industrial or therapeutic applications
  • Mesenchymal stem cell differentiation for cartilage regeneration
  • Pluripotent stem cell differentiation into various clinically relevant neuronal lineages

Dr. Tan Heng Liang

PhD in Medicine(2011), National University of Singapore, Singapore

Research Focus/Interests
  • Characterization of the cytotoxic antibody,mAb84, against hESC
  • Generation and characterization of novel antibodies targeting cancer surface antigens (Antibody Discovery Platform)
Jaichandran Sivalingam

Dr. Jaichandran Sivalingam

PhD in Biochemistry (2014), Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Research Focus/Interests

  • Differentiating induced pluripotent stem cells to erythrocytes
  • Targeted genome modification
  • Cell and gene therapy of genetic disorders 

Dr. Premkumar Jayaraman

PhD in Biotechnology (2013), Nanyang Technological University, Singapore

Research Focus/Interests
  • Scale-up of mesenchymal stem cells (MSCs) in suspension cultures using microcarrier-based technologies for industrial or therapeutic applications
  • Engineering MSCs for improved proliferation

Dr. Yu SuE

PhD in Biochemistry (2016), Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Research Focus/Interests
  • Therapeutic applications for Red blood cells and Mesenchymal Stem Cells (MSCs)
  • Cell therapy with tagging cells/stem cells

Year 2018

    Hossein Tavassoli, Sanaz Naghavi Alhosseini, Andy Tay, Peggy P.Y. Chan, Steve Kah Weng Oh and Majid Ebrahimi Warkiani (2018) Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products. Biomaterials 181: 333-346

    Qixing Zhong, Filip Laco, Mei-Chih Liao, Tsung Liang Woo, Steve Kah Weng Oh and Christina Li Lin Chai (2018) Influencing the fate of cardiac and neural stem cell differentiation using small molecule inhibitors of ALK5. STEM CELLS Translational Medicine 7(10): 709-720

    Esmond Lee, Jaichandran Sivalingam, Zhong Ri Lim, Gloryn Chia, Low Gin Shi, Mackenna Roberts, Yuin-Han Loh, Shaul Reuveny and Steve Kah Weng Oh (2018) Review: In vitro generation of red blood cells for transfusion medicine: Progress, prospects and challenges. Biotechnology Advances 36: 2118–2128

    Sherwin Ting, Alan Lam, Gerine Tong, Allen Chen, Heming Wei, JianJun Wu, Yue Ning Lam, Shaul Reuveny and Steve Oh (2018) Meticulous optimization of cardiomyocyte yields in a 3-stage continuous integrated agitation bioprocess. Stem Cell Research 31: 161-173

    Reza Moloudi, Steve Oh, Chun Yang, Kim Leng Teo, Alan Tin-Lun Lam, Majid Ebrahimi Warkiani and May Win Naing (2018) Inertial-Based Filtration Method for Removal of Microcarriers from Mesenchymal Stem Cell Suspensions. Scientific Reports 8: 12481

    Tan Heng Liang, Charlene Yong, Tan Bao Zhu, Fong Wey Jia, Jayanthi Padmanabhan, Angela Chin, Vanessa Ding, Ally Lau, Zheng Lu, Bi Xuezhi, Yang Yuansheng, Andre Choo (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Scientific Reports 8: 11608

    Filip Laco, Tsung Liang Woo, Qixing Zhong, Radoslaw Szmyd, Sherwin Ting, Fahima Jaleel Khan, Christina L. L. Chai, Shaul Reuveny, Allen Chen and Steve Oh (2018) Unraveling the Inconsistencies of Cardiac Differentiation Efficiency Induced by the GSK3β Inhibitor CHIR99021 in Human Pluripotent Stem Cells. Stem Cell Reports 10(6): 1851-1866

    Thomas Allison, Peter Andrews, Yishai Avior, Ivana Barbaric, Nissim Benvenisty, Christoph Bock, Jennifer Brehm, Oliver Brüstle, Ivan Damjanov, Andrew Elefanty, Daniel Felkner, Paul Gokhale, Florian Halbritter, Lyn Healy, Tim Xiaoming Hu, Barbara Knowles, Jeanne Loring, Tenneille Ludwig, Robyn Mayberry, Jameelah S. Mohamed, Suzanne Miacallef, Franz-Josef Müller, Christine Mummery, Norio Nakatsuji, Elizabeth Ng, Steve K. W. Oh, Orla O'Shea, Martin Pera, Benjamin Reubinoff, Paul Robson, Janet Rossant, Bernhard Schuldt, Davor Solter, Koula Sourris, Glyn Stacey, Edouard Stanley, Hirofumi Suemori, Kazutoshi Takahashi, and Shinya Yamanaka (2018) Assessment of established techniques to determine developmental and malignant potential of human pluripotent stem cells. Nature Communications 9(1): 1925

    Filip Laco, Tsung Liang Woo, Qixing Zhong, Radoslaw Szmyd, Sherwin Ting, Fahima Jaleel Khan, Christina L. L. Chai, Shaul Reuveny, Allen Chen and Steve Oh (2018) Unraveling the inconsistencies of cardiac differentiation efficiency induced by the GSK3β inhibitor CHIR99021 in human pluripotent stem cells. Stem Cell Reports 10: 1-16

    Reza Moloudi, Steve Oh, Chun Yang, Majid Ebrahimi Warkiani, and May Win Naing (2018) Inertial particle focusing dynamics in a trapezoidal straight microchannel: application to particle filtration. Microfluidics and Nanofluidics 22:33

    Esmond Lee, Zhong Ri Lim, Hong Yu-Chen, Bin Xia Yang, Alan Tin-Lun Lam, Allen Kuan-Liang Chen, Jaichandran Sivalingam, Shaul Reuveny, Yuin-Han Loh and Steve Kah-Weng Oh (2018) Defined serum free medium for bioreactor culture of an immortalized human erythroblast cell line. Biotechnology Journal 13(4): e1700567

    K P Myu Mai Ja, Kee Pah Lim, Allen Chen, Sherwin Ting, Shi Qi Li, Nicole Tee, Chrishan Ramachandra, Ashish Mehta, Philip Wong, Steve Oh & Winston Shim (2018) Construction of a Vascularized Hydrogel for Cardiac Tissue Formation in a Porcine Model. Journal of Tissue Engineering and Regenerative Medicine 12(4): e2029-e2038

Year 2017

    Jung-Hyun Kim, Andreas Kurtz, Bao-Zhu Yuan, Fanyi Zeng, Geoff Lomax, Jeanne F. Loring, Jeremy Crook, Ji Hyeon Ju, Laura Clarke, Maneesha S. Inamdar, Martin Pera, Meri T. Firpo, Michael Sheldon, Nafees Rahman, Orla O’Shea, Patricia Pranke, Qi Zhou, Rosario Isasi, Ruttachuk Rungsiwiwut, Shin Kawamata, Steve Oh, Tenneille Ludwig, Tohru Masui, Thomas J. Novak, Tsuneo Takahashi, Wataru Fujibuchi, Soo Kyung Koo, Glyn N. Stacey (2017) Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells. STEM CELLS Translational Medicine (Published Online)

    Asja T. Moerkamp, Hau Wan Leung, Noortje A.M. Bax, Stephanie Holst, Kirsten Lodder, Thijs Berends, Calinda K.E. Dingenouts, Andre Choo, Anke M. Smits and Marie‐Jose Goumans (2017) Glycosylated cell surface markers for the isolation of human cardiac progenitors. Stem Cells and Development 26(21): 1552-1565

    Lynn Y. W. Yap, Sadasivam Murali, Gajadhar Bhakta, Drew M. Titmarsh, Allen Kuan-Liang Chen, Lyn Chiin Sim, Muriel Bardor, Yu Ming Lim, James C.H. Goh, Steve K.W. Oh, Andre B.H. Choo, Andre J. van Wijnen, David E. Robinson, Jason D. Whittle, William R. Birch, Robert D. Short, Victor Nurcombe, Simon M. Cool (2017) Immobilization of vitronectin-binding heparan sulfates onto surfaces to support human pluripotent stem cells. Journal of Biomedical Materials Research Part B: Applied Biomaterials (Published Online)

    Lifeng Qiu, Mei-Chih Liao, Allen K. Chen, Shunhui Wei, Shaoping Xie, Shaul Reuveny, Zhi Dong Zhou, Walter Hunziker, Eng King Tan, Steve K.W. Oh and Li Zeng (2017) Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson’s Disease. Stem Cells Translational Medicine (Published Online)

    Youshan Melissa Lin, Jialing Lee, Jessica Fang Yan Lim, Mahesh Choolani, Jerry Kok Yen Chan, Shaul Reuveny and Steve Kah Weng Oh (2017) Critical attributes of human early mesenchymal stromal cells-laden microcarrier constructs for improved chondrogenic differentiation. Stem Cell Research & Therapy 8: 93

    Matthew S. F. Choo, Vanessa Ding, Heng Liang Tan, Brian Liau, Lauren Hartley-Tassell, Roberto Castangia, Omar Belgacem, Stuart M. Haslam, Anne Dell and Andre B. H. Choo (2017) Characterization of H Type 1 and Type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4. Journal of Biological Chemistry 292(15): 6163-6176

    Yiu-Wing Kam, Cheryl Yi-Pin Lee, Teck-Hui Teo, Shanshan W. Howland, Siti Naqiah Amrun, Fok-Moon Lum, Peter See, Nicholas Qing-Rong Kng, Roland G. Huber, Mei-Hui Xu, Heng-Liang Tan, Andre Choo, Sebastian Maurer-Stroh, Florent Ginhoux, Katja Fink, Cheng-I Wang, Lisa F.P. Ng, and Laurent Rénia (2017) Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections. JCI Insight 2(8): e92428

    Jian Li, Alan Tin-Lun Lam, Jessica Pei Wen Toh, Shaul Reuveny, Steve Kah-Weng Oh and William R. Birch (2017) Tunable Volumetric Density and Porous Structure of Spherical Poly-ɛ-caprolactone Microcarriers, as Applied in Human Mesenchymal Stem Cell Expansion. Langmuir 33(12): 3068–3079

    Alan Tin-Lun Lam, Jian Li, Jessica Pei-Wen Toh, Eileen Jia-Hui Sim, Allen Kuan-Liang Chen, Jerry Kok-Yen Chan, Mahesh Choolani, Shaul Reuveny, William R. Birch and Steve Kah-Weng Oh (2017) Biodegradable poly-ε-caprolactone microcarriers for efficient production of human mesenchymal stem cells and secreted cytokines in stirred bioreactors. Cytotherapy 19(3): 419-432

    Jiyun Zheng, Tan Heng Liang, Paul Matsudaira and Andre Choo (2017) Excess reactive oxygen species production mediates monoclonal antibody-induced human embryonic stem cell death via oncosis. Cell Death and Differentiation 1–13

    Maximilian Klement, Jiyun Zheng, Chengcheng Liu, Victor Vai-Tak Wong, Andre Boon-Hwa Choo, Dong-Yup Lee and Dave Siak-Wei Ow (2017) Antibody engineering of a cytotoxic monoclonal antibody 84 against human embryonic stem cells: Investigating the effects of multivalency on cytotoxicity. Journal of Biotechnology 243: 29–37

Year 2016

    Asha Shekaran, Alan Lam, Eileen Sim, Lee Jialing, Li Jian, Jessica Toh Pei Wen, Jerry Kok Yen Chan, Mahesh Choolani, Shaul Reuveny, William Birch and Steve Oh (2016) Biodegradable ECM-Coated PCL Microcarriers Support Scalable Human Early MSC Expansion and in vivo Bone Formation. Cytotherapy 18(10): 1332-1344

    Jaichandran Sivalingam, Alan Tin-Lun Lam, Hong Yu Chen, Bin Xia Yang, Allen Kuan-Liang Chen, Shaul Reuveny, Yuin-Han Loh and Steve Kah-Weng Oh (2016) Superior red blood cell generation from human pluripotent stem cells via a novel microcarrier based embryoid body platform. Tissue Engineering Part C: Methods 22(8): 765-780

    Hock Chuan Yeo, Sherwin Ting, Romulo Martin Brena, Geoffrey Koh, Allen Chen, Siew Qi Toh, Yu Ming Lim, Steve Kah Weng Oh and Dong-Yup Lee (2016) Genome-Wide Transcriptome and Binding Sites Analyses Identify Early FOX Expressions for Enhancing Cardiomyogenesis Efficiency of hESC Cultures. Scientific Reports 6: 31068

    Youshan Melissa Lin, Jessica Fang Yan Lim, Jialing Lee, Mahesh Choolani, Jerry Kok Yen Chan, Shaul Reuveny, Steve Kah Weng Oh (2016) Expansion in microcarrier-spinner cultures improves the chondrogenic potential of human early mesenchymal stem cells. Cytotherapy 18: 740-753

    Lifeng Qiu, Yu Ming Lim, Allen K Chen, Shaul Reuveny, Steve K.W. Oh, Eng King Tan, Li Zeng (2016) Microcarrier-expanded Neural Progenitor Cells can Survive, Differentiate, and Innervate Host Neurons Better when Transplanted as Aggregates. Cell Transplantation 25(7): 1343-1357

    Jaichandran Sivalingam, Dimitar Kenanov, Hao Han, Ajit Johnson Nirmal, Wai Har Ng, Sze Sing Lee, Jeyakumar Masilamani, Toan Thang Phan, Sebastian Maurer-Stroh & Oi Lian Kon (2016) Multidimensional genome-wide analyses show accurate FVIII integration by ZFN in primary human cells. Molecular Therapy 24(3): 607-619

Year 2015

    Kah Yong Tan, Shaul Reuveny, Steve Kah Weng Oh (2015) Recent advances in serum-free microcarrier expansion of mesenchymal stromal cells: Parameters to be optimized. Biochemical and Biophysical Research Communications Open Access Review Paper pii: S0006-291X(15)30595-30597

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