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World J Stem Cells. Dec 31, 2009; 1(1): 11-21
Published online Dec 31, 2009. doi: 10.4252/wjsc.v1.i1.11
Embryoid body formation from embryonic and induced pluripotent stem cells: Benefits of bioreactors
Sasitorn Rungarunlert, Mongkol Techakumphu, Melinda K Pirity, Andras Dinnyes
Sasitorn Rungarunlert, Agricultural Biotechnology Center, H-2100 Gödöllö, Hungary
Sasitorn Rungarunlert, Andras Dinnyes, Molecular Animal Biotechnology Laboratory, Szent Istvan University, H-2100 Gödöllö, Hungary
Sasitorn Rungarunlert, Mongkol Techakumphu, Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
Melinda K Pirity, Andras Dinnyes, BioTalentum Ltd., Aulich Lajos u. 26. H-2100, Gödöllö, Hungary
Author contributions: Rungarunlert S conceived the idea and prepared the original draft; The other authors contributed equally to the final manuscript of this review.
Supported by Grants from EU FP6 (“MEDRAT”- LSHG-CT-2005-518240; “CLONET”, MRTN-CT-2006-035468), EU FP7 (“PartnErS”, PIAP-GA-2008-218205; “InduHeart”, EU FP7-PEOPLE-IRG-2008-234390; “InduStem”, PIAP-GA-2008-230675; “Plurisys”, HEALTH-F4-2009-223485); NKFP_07_1-ES2HEART-HU, No. OM-00202-2007 and CHE-TRF senior scholarship, No. RTA 5080010. Rungarunlert S was supported by grant under the program Strategic Scholarships for Frontier Research Network for the Joint Ph.D., and Program Thai Doctoral degree from the Office of the Higher Education Commission, Thailand, No. CHE-PhD-SW-2005-100
Correspondence to: Andras Dinnyes, DSc, Professor, BioTalentum Ltd., Aulich Lajos u. 26. H-2100, Gödöllö, Hungary.
Telephone: +36-20-5109632 Fax: +36-28-526243
Received: December 1, 2009
Revised: December 14, 2009
Accepted: December 21, 2009
Published online: December 31, 2009

Embryonic stem (ES) cells have the ability to differentiate into all germ layers, holding great promise not only for a model of early embryonic development but also for a robust cell source for cell-replacement therapies and for drug screening. Embryoid body (EB) formation from ES cells is a common method for producing different cell lineages for further applications. However, conventional techniques such as hanging drop or static suspension culture are either inherently incapable of large scale production or exhibit limited control over cell aggregation during EB formation and subsequent EB aggregation. For standardized mass EB production, a well defined scale-up platform is necessary. Recently, novel scenario methods of EB formation in hydrodynamic conditions created by bioreactor culture systems using stirred suspension systems (spinner flasks), rotating cell culture system and rotary orbital culture have allowed large-scale EB formation. Their use allows for continuous monitoring and control of the physical and chemical environment which is difficult to achieve by traditional methods. This review summarizes the current state of production of EBs derived from pluripotent cells in various culture systems. Furthermore, an overview of high quality EB formation strategies coupled with systems for in vitro differentiation into various cell types to be applied in cell replacement therapy is provided in this review. Recently, new insights in induced pluripotent stem (iPS) cell technology showed that differentiation and lineage commitment are not irreversible processes and this has opened new avenues in stem cell research. These cells are equivalent to ES cells in terms of both self-renewal and differentiation capacity. Hence, culture systems for expansion and differentiation of iPS cells can also apply methodologies developed with ES cells, although direct evidence of their use for iPS cells is still limited.

Keywords: Embryoid body, Embryonic stem cells, Induced pluripotent stem cells, Bioreactors, Differentiation