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  • Review: In vitro generation of red blood cells for transfusion medicine: Progress, prospects and challenges. Biotechnology advances Lee, E., Sivalingam, J., Lim, Z. R., Chia, G., Shi, L. G., Roberts, M., Loh, Y., Reuveny, S., Oh, S. K. 2018

    Abstract

    In vitro generation of red blood cells (RBCs) has the potential to circumvent the shortfalls in global demand for blood for transfusion applications. The conventional approach for RBC generation has been from differentiation of hematopoietic stem cells (HSCs) derived from cord blood, adult bone marrow or peripheral blood. More recently, RBCs have been generated from human induced pluripotent stem cells (hiPSCs) as well as from immortalized adult erythroid progenitors. In this review, we highlight the recent advances to RBC generation from these different approaches and discuss the challenges and new strategies that can potentially make large-scale in vitro generation of RBCs a feasible approach.

    View details for PubMedID 30273713

  • Defined serum free medium for bioreactor culture of an immortalized human erythroblast cell line. Biotechnology journal Lee, E. n., Lim, Z. R., Yu-Chen, H. n., Yang, B. X., Lam, A. T., Chen, A. K., Sivalingam, J. n., Reuveny, S. n., Loh, Y. H., Oh, S. K. 2018

    Abstract

    Anticipated shortages in donated blood supply have prompted investigation of alternative approaches for in-vitro production of red blood cells (RBCs), such as expansion of conditional immortalization erythroid progenitors. However, there is a bioprocessing challenge wherein factors promoting maximal cell expansion and growth-limiting inhibitory factors are yet to be investigated. We used an erythroblast cell line (ImEry) derived from immortalizing CD71+CD235a+ erythroblast from adult peripheral blood for optimization of expansion culture conditions. Design of Experiments (DOE) was used in media formulation to explore relationships and interactive effects between factors which affect cell expansion. Our in-house optimized medium formulation produced significantly higher cell densities (3.62 0.055) x106 cells/mL, n=3) compared to commercial formulations (2.07 0.055) x106 cells/mL, n=3; at 209 hour culture). Culture media costs per unit of blood was shown to have a 2.96 - 3.09 times cost reduction. As a proof of principle for scale up, ImEry were expanded in a half-litre stirred-bioreactor under controlled settings. Growth characteristics, metabolic and molecular profile of the cells were evaluated. ImEry had identical O2 binding capacity to adult erythroblasts. Amino acid supplementation resulted in further yield improvements. Our study serves as a first step for scaling up erythroblast expansion in controlled bioreactors.

    View details for PubMedID 29330927

  • Decellularized material as scaffolds for tissue engineering studies in long gap esophageal atresia EXPERT OPINION ON BIOLOGICAL THERAPY Lee, E., Milan, A., Urbani, L., De Coppi, P., Lowdell, M. W. 2017; 17 (5): 573-584

    Abstract

    Esophageal atresia refers to an anomaly in foetal development in which the esophagus terminates in a blind end. Whilst surgical correction is achievable in most patients, when a long gap is present it still represents a major challenge associated with higher morbidity and mortality. In this context, tissue engineering could represent a successful alternative to restore oesophageal function and structure. Naturally derived biomaterials made of decellularized tissues retain native extracellular matrix architecture and composition, providing a suitable bed for the anchorage and growth of relevant cell types. Areas covered: This review outlines the various strategies and challenges in esophageal tissue engineering, highlighting the evolution of ideas in the development of decellularized scaffolds for clinical use. It explores the interplay between clinical needs, ethical dilemmas, and manufacturing challenges in the development of a tissue engineered decellularized scaffold for oesophageal atresia. Expert opinion: Current progress on oesophageal tissue engineering has enabled effective repair of patch defects, whilst the development of a full circumferential construct remains a challenge. Despite the different approaches available and the improvements achieved, a gold standard for fully functional tissue engineered oesophageal constructs has not been defined yet.

    View details for DOI 10.1080/14712598.2017.1308482

    View details for Web of Science ID 000399490700006

    View details for PubMedID 28303723

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