Embed Size (px)
Citation preview
E D I T O R I A L
www.ScienceTranslationalMedicine.org 16 October 2013 Vol 5 Issue 207 207ed17 1
T R A N S L AT I O N A L C H A L L E N G E S
SCIENTISTS HAVE RECOGNIZED THE POTENTIAL OF EMBRYONIC STEM CELLS TO REVolutionize 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 f eld of regenerative medicine (1). T e 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 VINET e workshop focused primarily on stem cell engineering R&D in North America. T e 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.
Def ning 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 inf uential components in the stem cell microenvironment. T ese issues are only amplif ed when one endeavors to create stem cell therapies or functional hu-man tissues for clinical use. T erefore, the research community and funding agencies should begin by investing their resources in the development of def nitions for specif c cell pheno-types, standards for characterizing cell types, and benchmarks to def ne the functional state of cells, all of which must be accepted by the stem cell engineering f eld at large. T is ef ort must occur before we will be able to (i) characterize and manipulate stem and progenitor cell phenotypes at will, (ii) def ne the microenvironment and its impact on cell phenotype, (iii) control purity and heterogeneity in stem cell populations, (iv) address scientif c and biomanufacturing issues associated with expansion of cell populations and neotissue forma-tion, and (v) assess and predict the ef cacy of stem cell–based therapies. T ese 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 dif erent 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-def ned product. Biomanufacturing of stem cell products is fundamentally dif erent 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 dif cult to stringently def ne (as an example, relative to a biological molecule with a def nitive 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, purif cation, 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: [email protected]
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: [email protected]
on
Oct
ober
18,
201
3st
m.s
cien
cem
ag.o
rgD
ownl
oade
d fr
om
on
Oct
ober
18,
201
3st
m.s
cien
cem
ag.o
rgD
ownl
oade
d fr
om
E D I T O R I A L
www.ScienceTranslationalMedicine.org 16 October 2013 Vol 5 Issue 207 207ed17 2
packaging) that also can limit the yield and production ef ciency of stem cell–based thera-peutics. Emerging engineering technologies for label-free characterization and hands-free robotic manufacturing may lead to the optimization of downstream processes.
Biological models. Microphysiological organs—commonly called “organs on a chip”—represent an enabling technology expected to accelerate drug development and toxicity screening. T e challenge in engineering a tissue at the microscale level involves dif erentiat-ing stem cells into the cells necessary to simulate an organ, creating conditions in which the cells self-assemble into the desired microphysiological structure, and encouraging cells on a chip to communicate with one another continuously as a microphysiological system. Ad-vances in microf uidic systems and biomaterials coupled with new biosensors will be critical for forming more complete microphysiological systems.
Forging a fusion f eld. Participants in the workshop identif ed the emergent f eld of immunoengineering as crucial for regenerative medicine. T is discipline involves the appli-cation of engineering approaches and principles to quantitatively study the immune system in health and disease and to develop therapeutic interventions for precisely controlling and modulating a patient’s immune response. T ere are a variety of challenges here; however, the fundamental issue is enabling the immunoacceptance of stem cells that are not derived from the patient. As an example, strategies are needed to optimize the survival and engraf ment of stem cells and to understand the ef ects of immune responses on multiple dosing. Also required are methods for quantitative, high-throughput assessment of the immune status of patients, an area in which engineers can contribute.
Engineering a new economy. All of the aforementioned areas identify opportunities for engineering approaches to make seminal contributions to the therapeutic ef orts of the global stem cell research community. Furthermore, an increase in the involvement of bio-engineers and engineering approaches in the stem cell f eld is expected to result in the fol-lowing tangible outcomes:
• A quantitative understanding of basic stem cell biology.
• Tools for both basic research and the translation of basic science into stem cell–based therapeutic applications.
• Acceleration in the development of new therapeutic products, while at the same time reducing the costs of development processes.
• T e ability to address diseases and injuries for which there are currently no ef ective treatment options through the development of stem cell–based therapies (here, a holy grail is the treatment of neurodegenerative diseases).
• Translation of stem cell technologies into commercial products that will contribute to the growth of the 21st-century bioeconomy around the world.
1. New Directions in Tissue Engineering and Regenerative Medicine conference, Sonoma, CA, 10 to 13 July 2013; http://scec.gatech.edu/new-directions.
Acknowledgments: The Sonoma, California, workshop was supported by NSF grant CBET–1343937; the universities of the coau-thors; the University of Maryland, College Park; and Cedars-Sinai Medical Center.
– Kevin E. Healy, Todd C. McDevitt, William L. Murphy, Robert M. Nerem
