This document describes a brief plan for a worldwide assessment of the R&D in Stem Cells Engineering (SCE). The study is aimed at determining the status and trends of research and development in this field in the leading laboratories and organizations via an on-site peer review process developed at the World Technology Evaluation Center (WTEC), Inc. WTEC is a non-profit 501(c)(3) research institute, which is a spin-off of Loyola University Maryland. Since 1989, WTEC has provided such assessment studies in more than 60 fields of R&D under peer-reviewed grants from NSF. Other agencies, including several institutes of NIH, NASA, NIST, FDA, and various offices from DOE and DOD, have co-sponsored these studies with financial support through interagency transfers to NSF. Recent WTEC studies related to this study include: Mobility Research (2011), Nanotechnology 2011, Brain-Computer Interfaces 2007, Systems Biotechnology 2004, Biosensing 2003, and Tissue Engineering (2003). Final reports from these and all the other WTEC studies are posted at: http://www.wtec.org
A preliminary workshop on Stem Cell Research for Regenerative Medicine (RM) and Tissue Engineering (TE)(1) was held at NSF on February 1-2, 2007. It was sponsored by NSF and NIH and facilitated by WTEC. The workshop speakers presented an overview of the research activities in North America. The workshop confirmed the increasing convergence of these research areas in the drive toward clinical solutions for the deterioration of various human organs impacted by injury or disease. The workshop revealed that, although substantial research has been accomplished, there was much to be done to meet any expectations of completed translations for improvement of human health and commercial success. It was also clear that there was much to be learned abroad--other nations have been making rapid progress while the US research community has been handicapped by Federal restrictions. (1)
In May 2010, NSF and others funded the Second International Conference on Stem Cell Engineering in Boston, MA. The conference emphasized how research in stem cell biology and engineering can combine to aid in the development of stem cell therapeutics and bioprocesses (2). The goal of the conference was to accelerate progress towards innovative solutions to basic and translation problems in regenerative medicine. Topics emphasized how quantitative approaches could yield an increased understanding of the biological mechanisms that underlie these stem cell fate choices, cancer stem cells, induced pluripotent (iPS) stem cells, technologies to study stem cell function, and the development of bioprocesses to culture stem cells for commercial applications.
Bibliometric studies show the skyrocketing interest in the field-from 360 papers worldwide in 2005 to almost 1000 four years later. The US leads the world in stem cell engineering, but not by much: the EU as a whole is essentially equal to the US, as is a group of five top Asian countries. There are clearly valuable opportunities to learn from research in stem cell engineering overseas.
The tiny island-state of Singapore offers a remarkable example of what can be accomplished in research with a combination of dedication, generous funding, and an enlightened attitude towards research. A recent study in the leading industry journal Cell Stem Cell, ranked Singapore fourth behind Britain, Israel and China, after looking at papers published on breakthroughs in the field. Ironically, the study identified the US, France and Japan as underperformers. These three nations have one thing in common - an uncertain research environment arising from the protracted policy debates over ethical issues surrounding stem cells (3).
This paper presents a brief concept, by which WTEC offers to
conduct a worldwide assessment of the current status and the
trends of stem cell engineering. The objectives of an
international assessment would be to:
* Guide and justify U. S. research investments
* Look for good ideas abroad (technology transfer)
* Look for opportunities for cooperation and collaboration
* Compare U.S. R&D programs and status with those abroad
The February 2007 workshop provides a head start for the assessment study, by reviewing U.S. and Canadian research in the field and framing issues to determine progress in the field. A panel of U.S. experts, suggested by sponsoring agencies and recruited by WTEC, will build on these findings by peer reviews of research abroad, visiting the sites of the research institutions and researchers who are noted for the most advanced work in Europe and Asia.
Knowledge of research activities abroad will assist in formulation and prioritization of research directions to support President Obama's Executive Order for expanding stem cell research(4) with the greatest potential for clinical benefit. The President, Congress, and numerous states have recognized the value of stem cell research. The Administration requested for FY2011 increases overall funding on stem cell research from $30 million to $1.1 billion. (5) Individual states of the U.S have committed approximately $4.2 billion over the next five to ten years for furthering research in stem cells in prospect of important industries and health benefits arising. Dozens of companies have already entered the field to provide equipment and to produce clinical and experimental stem cells. There is clear impetus for support of stem cell research for the continued leadership of America in basic science and for the betterment of humankind. A Congressional Research Service Report on Stem Cell Research (6) , in addition to reviewing the political, moral and ethical issues of the subject, clearly indicates the strengthening interest and economic commitment for stem cell research in the U.S. and the rest of the world.
Successful research in the application of research in stem cell engineering will cross multiple disciplines and make use of advances in systems biology, the human genome, medical informatics, systems engineering, biochemistry, biomedical engineering, and basic medicine, chemistry, and biology.
This study will use WTEC's methodology of
an expert panel to conduct site visits to overseas
laboratories where the best work in SCE is done. This effort
will be combined with the Panel's own research and
assessments. The findings of this study will result in
deliverables consisting of briefings to sponsors, public
workshops, and a final report. Collectively they should
provide a comprehensive, peer-reviewed set of evaluations of
SCE R&D overseas, compared to those in the United States.
There are a number of expected benefits from such a study. One important benefit will come from the process itself. Interested programs across NSF and from other agencies will be working together to better define the field and its needs together. Using the findings of this study and other inputs they can collectively work out a research directions roadmap for future SCE research and education. A new vision and level of energy may emerge from the government and research community as a result.
There will be other tangible benefits. For example, the study is a great vehicle to address some of the key issues of critical importance to programs officers and the research community, including:
* What is the position of foreign R&D in SCE relative to the United States?
* What are the barriers and gaps of research in SCE we can learn from overseas?
* What are the major innovations and emerging ideas that are worth exploring here in the United States?
* What are the opportunities for international collaboration to tackle bigger technical challenges by combining complementary resources and strengths?
- To obtain the intended benefits, this
study will focus on a range of issues whose R&D
activities abroad will best inform our own government
programs and the research community of the challenges,
barriers, and opportunities in SCE. The study panel,
under the guidance of the sponsors, will be instrumental
in helping to develop a definitive scope of the study.
Among these objectives related to the proposed study
* Understanding and controlling the signals for cellular response.
* Formulating biomaterial scaffolds and the tissue matrix environment.
* Developing enabling tools.
* Promoting scale-up, translation, and commercialization.
Finally, beyond the above technical issues, the study may also address the following broader issues:
* Mechanisms for enhancing international and interdisciplinary cooperation in the field
* Opportunities for shortening the lead time for deployment of new SCRMTE technologies emerging from the laboratory
* Long range research, educational, and infrastructure issues that need addressed to promote better progress in the field
* Current government R&D funding levels overseas compared to the United States, to the extent data are available
Other more specific issues and topics which might be considered are:
* designer stem cells for physical modeling of disease and cancer
* computer modeling of stem cell transformation to organ tissue
* computer modeling of culturing production processes
* 3-D computer models of physiology
* tissue compatibility and rejection mechanisms
* characterization of stem cells (physical, chemical, biological): international standards for description and measurement, measurement sensors and systems
* research on stem cells for drug development
* standards for experiments and testing
* education of researchers, technicians, and clinicians
* acceleration of lab results to industrial scale
* efficient pathways to approval for clinical use
* patents and intellectual property rights
* government support and policies
The above lists of topics will be refined by panel members in consultation with the sponsors at the study kickoff meeting.
- Task 1
The contractor, in consultation with study sponsors, shall select a panel of six (6) U.S. experts in the field who are familiar with the technology elements listed above for SCE R&D and who are also current in international activities in the field. The panel chair shall have sufficient stature in this field to command respect in recruitment of panelists, and make presentations of results to his or her peers. The chair also will have the necessary skills at leading a panel to efficiently conduct the study. The contractor will conclude standard consulting contracts with these panelists for their work, including bonuses for timely delivery of their reports.
- Task 2
The panel shall be organized at a kick-off meeting to be held in the Washington, DC area. The chair will define the scope of the study (with guidance from all of the agency sponsors) and assign each panelist a section of the final report based on his or her area of expertise within the field. A schedule for the study will be established, including dates for the workshop and completion of the final report. During the preliminary study, the contractor shall assist the panelists by conducting electronic literature searches and by acquiring, extracting, and reproducing relevant literature. Passworded and public Web sites will be established and maintained by the contractor during the course of the study as needed to facilitate the work of the panel.
- Task 3
It has been proven in previous R&D assessments that visits to foreign laboratories greatly improve the amount, accuracy, and timeliness of the information available to the panelists. Thus, the contractor shall organize a fact-finding trip for the panel to visit centers of excellence in SCE R&D at selected sites abroad. WTEC has found that professional advance work for these trips is highly beneficial, thus allowances for advance work to be performed by proven performers are included in the recommended budget. This budget assumes that the panel will travel to Asia and Western Europe; other regions may also be considered if the budget permits.
- Task 4
The contractor shall organize a workshop in the Washington, DC area for the presentation of the results. Approximately 40 key participants from government and the private sector would be expected to attend a one-day presentation and discussion of the results. Each panelist will make a 30-minute presentation with visual aids of his or her findings, and the chair will make an overall summary. Copies of the visual aids will be available at the workshop meeting.
The workshop will also be webcast, allowing live remote viewing of the workshop. The webcast will also be archived, permitting viewing of the workshop over an indefinite period following the conclusion of the workshop.
- Task 5
The contractor shall produce a final written report detailing the findings and distribute it to study participants, hosts, and sponsors. The contractor may also find appropriate professional society or commercial publishers suitable for optimal distribution to the research community and the public. The study shall be completed within eighteen (18) months after project initiation (API).
- Task 6
The contractor shall convert the complete final written report into Adobe Acrobat (pdf) format (including all graphics and tables) and make it available on the WTEC Web server and on CD-ROM.
The schedule for the study will be determined at the kickoff meeting by mutual agreement of the sponsors, the WTEC staff, and the panel members. However, a typical schedule and associated deliverables is shown below. The term "or" means the latter of two events. The schedule presented below is a plan for finishing the study in 12 months, although 18 months is allowed under paragraph 4.5 above to allow time for dissemination activities that may extend for some months after the report is complete.
- * kickoff meeting -- approximately two months after project initiation (API) (delivery of draft scope of panel work and panelist data)
- * foreign site visits completed -- approximately five months API
- * draft site reports from the site visits - approximately six months API or within six weeks after the last site visits
- * final workshop -- approximately seven months API or within two months after the last site visits (hard copies of presentation material delivered and posted on Web shortly thereafter)
- draft analytical report -- approximately ten months API or three months after the workshop
- * f. final report -- approximately twelve months API or two months after the draft report is sent to the site visit hosts for review (printed version, 75 copies total, simultaneously placed in PDF form on a CD and the WTEC public Web site -- the primary means of dissemination). Depending on availability of funds, WTEC also will seek opportunities for commercial or professional society publication of a higher-quality version of the final report.
The budget for this study will be determined by the geographic and technical scope desired by the sponsors. The level of effort can be estimated from WTEC's experience with more than 60 such studies. For example, a recent study of rapid vaccines manufacturing in Asia with a panel of six experts cost about $309K. A study of simulation-based engineering and science with nine panelists covering 59 sites in Asia and Europe cost about $750K.
If the sponsors decide to include add additional panelists or areas to be visited, additional cost will be incurred, as determined by the level of work involved. Other options include a senior advisory committee and a possible research directions workshop to follow the international technology assessment--to plan the research agenda for a possible national initiative.
- Shoichet, Molly and Caplan, Arnold (co-chairs)Workshop Final Proceedings, Stem Cell Research for Regenerative Medicine and Tissue Engineering, February 1-2, 2007, Baltimore: WTEC http://www.wtec.org/stem_cell_workshop/
- Zandstra, Peter and Daley, George (co-chairs), SBE's Second International Conference on Stem Cell Engineering, May 2-5, 2010, Boston, MA., http://www.aiche.org/sbe/events/stemcelleng.aspx
Robert M. Nerem,
Georgia Institute of Technology
University of California, Berkeley
- Peter Zandstra
University of Toronto
- Sean Palecek,
University of Wisconsin
- Todd McDevitt,
Emory Univ./Georgia Tech