EDITORIAL www.ScienceTranslationalMedicine.org 16 October 2013 Vol 5 Issue 207 207ed17 1 TRANSLATIONAL CHALLENGES SCIENTISTS HAVE RECOGNIZED THE POTENTIAL OF EMBRYONIC STEM CELLS TO REV olutionize modern medicine since their emergence two decades ago. Still, few products have negotiated the arduous path to clinical application. Biomedical science now stands at the threshold of realizing stem cell–based therapies and validating their contribution to clini- cal medicine. Crossing the threshold will require interdisciplinary collaborations in which bioengineers and engineering approaches play an increasingly prominent role. To this end, the National Science Foundation (NSF) sponsored a recent workshop in the Sonoma, Cali- fornia wine country that focused on the application of engineering principles to the feld of regenerative medicine (1). Te workshop resulted in recommendations to address a list of grand challenges described in detail in an NSF report. Here, we summarize the report’s key elements. FUTURE GOALS—FRESH OFF THE VINE Te workshop focused primarily on stem cell engineering R&D in North America. Te group pinpointed challenges in addressing key knowledge gaps and in translational (pro- cessing, commercialization, and regulatory) bottlenecks and then discussed engineering ap- plications designed to tackle these diverse and complex challenges. Defning a starting point. Progress in basic stem cell biology is challenged by the wide range of observable stem cell phenotypes documented in the literature, coupled with the diversity of biologically infuential components in the stem cell microenvironment. Tese issues are only amplifed when one endeavors to create stem cell therapies or functional hu- man tissues for clinical use. Terefore, the research community and funding agencies should begin by investing their resources in the development of defnitions for specifc cell pheno- types, standards for characterizing cell types, and benchmarks to defne the functional state of cells, all of which must be accepted by the stem cell engineering feld at large. Tis efort must occur before we will be able to (i) characterize and manipulate stem and progenitor cell phenotypes at will, (ii) defne the microenvironment and its impact on cell phenotype, (iii) control purity and heterogeneity in stem cell populations, (iv) address scientifc and biomanufacturing issues associated with expansion of cell populations and neotissue forma- tion, and (v) assess and predict the efcacy of stem cell–based therapies. Tese multicom- ponent bottlenecks that limit our understanding of stem cell biology and advances in thera- peutic development are ideally suited for integrative stem cell–engineering approaches. Computational modeling. It is clear that the essential enabling technologies must take diferent forms. For example, computational modeling will help to improve our un- derstanding of the hierarchical symphony of signals that control stem cell fate and function. As a result, scientists will be able to devise computational models based on environmental and initial-state parameters that permit the prediction of phenotypic states and transitions. Computational models also will have a central role in another enabling technology, bio- manufacturing, which involves the design and development of instruments and processes for the manufacturing of products. Modeling will help scientists to design feedback controls for stem cell processing systems. Stem cell biomanufacturing. New technologies also are needed to address bottlenecks in stem cell biomanufacturing—the actual production, packaging, and delivery of a well- defned product. Biomanufacturing of stem cell products is fundamentally diferent from the manufacturing of vaccines and biologics because in these latter cases, cells simply serve as the vehicle to produce the product, whereas for stem cell biomanufacturing, the cells are the product. Cells as products are more difcult to stringently defne (as an example, relative to a biological molecule with a defnitive molecular weight and biological activity), and the multipotency of stem cell products creates singular challenges as a result of the cells’ ability to dynamically vary their properties and potential. Most of the research to date has focused on the upstream steps of the biomanufacturing processes (such as stem or progenitor cell isolation and culture conditions for cell maintenance and expansion) rather than equally important downstream processes (such as cell harvesting, concentration, purifcation, and Engineering the Emergence of Stem Cell Therapeutics Kevin E. Healy is the Jan Fandrianto Distinguished Chair, Department of Bioen- gineering, University of California at Berkeley, Berkeley, CA 94720, USA. Citation: K. E. Healy, T. C. McDevitt, W. L. Murphy, R. M. Nerem, Engineering the emergence of stem cell therapeutics. Sci. Transl. Med. 5, 207ed17 (2013). 10.1126/scitranslmed.3007609 Todd C. McDevitt is Associate Professor in the Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, and Director, Stem Cell Engineering Center, Georgia Institute of Technol- ogy, Atlanta, GA 30332, USA. William L. Murphy is the Harvey D. Spangler Professor, Biomedical Engineering, and Co-Director, Stem Cell and Regenerative Medicine Cen- ter, University of Wisconsin– Madison, Madison, WI 53705, USA. E-mail: wlmurphy@ wisc.edu Robert M. Nerem is Parker H. Petit Distinguished Chair for Engineering in Medicine and Institute Professor Emeritus, and Founding Director of the Petit Institute for Bioen- gineering and Bioscience, Georgia Institute of Technol- ogy, Atlanta, GA 30332, USA. E-mail: robert.nerem@ibb. gatech.edu on October 18, 2013 stm.sciencemag.org Downloaded from on October 18, 2013 stm.sciencemag.org Downloaded from