Mahendra Rao, MD, PhD
Director, NIH Center for Regenerative Medicine (NIH CRM)
Dr. Rao indicated no relevant conflicts of interest.
Every once in a great while, a scientific discovery is truly galvanizing. In the field of regenerative medicine, such an event occurred in 2006 with the discovery of a method to generate induced pluripotent stem cells (iPSCs). The finding that four transcription factors (and in some cases fewer) are sufficient to convert an adult human somatic cell into an embryonic stem cell-like state created a slip stream that has accelerated the pace of growth of personalized medicine. This imaginative technological achievement, replicated by hundreds of laboratories worldwide, provided a mechanism for generating novel cell lines carrying different disease mutations, thereby opening the way for experiments that were previously thought to be impossible. The combination of iPSC technology, advances in next-generation sequencing, and the ability to modulate or engineer the genome with high efficiency put biomedical science on the cusp of a fundamental change in approach to experimental design. The National Institutes of Health (NIH) recognized this unique position and developed a strategy to address the impending paradigm shift in human biology research. Following a thorough canvassing of the field, NIH created the Common Fund initiative from which arose, in 2010, the Center for Regenerative Medicine (NIH CRM).1
The Center’s mandate is to accelerate, responsibly, stem cell technology toward therapeutic applications. To achieve this goal, the Center needed to identify and resolve roadblocks to progress and optimally utilize existing resources. The following two major problems were targeted: 1) lack of agreed-upon standards and 2) absence of a coordinated funding strategy.
Standardization is most needed in the areas of patient consent, cell line development, and access to uniform controls.2,3 A broadly applicable consent form was developed based on input both from experts in the field and from institutional review boards. Under the auspices of CRM, well-characterized cell lines, controls, and reagent standards were obtained from both academic collaborators and commercial vendors and made available for dissemination to the scientific community. In tandem, protocols for generating, characterizing, and differentiating cell lines were compiled for use by investigators, and in an ongoing process, the Center is working with the FDA Stem Cell Task Force to develop and certify clinical-grade cell lines and controls intended for use in clinical trials.
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Coordination of funding has been particularly challenging because stem cell research has been the focus of major support initiatives at the state level, each program with its own mandate and administrative process. While the state funding initiatives are generally beneficial for the field, minimizing programmatic redundancies will reduce cost and increase efficiency. Given California’s prominent and successful voter-funded program, the Center has taken the first step toward addressing state-level coordination by forging collaboration between NIH and the California Institute for Regenerative Medicine (CIRM). With CIRM, we are focusing primarily on Parkinson’s disease and retinal pigment epithelium biology. A planned outgrowth of this collaborative effort is the development of standardized methods and research tools that then become available to other investigators. In this way, the program serves as a technology conduit for the broader regenerative medical community. The Center continues to explore similar alliances with other state agencies with the goal of encouraging and supporting promising therapeutic initiatives.
Inter-governmental partnership is also part of CRM’s developmental strategy as the Center is uniquely positioned to facilitate interactions that are not feasible at the institutional or even the state level. For example, CRM, in cooperation with the NIH Fogarty International Center, is exploring collaborative opportunities with other international centers of stem cell biology, including those in India and Korea. Similarly, the Center has had success in establishing agreements at the institutional level with stem cell research groups, both in the United States and abroad. Notably, a memorandum of understanding has been put in place with both iCeMS at Kyoto University in Japan and with Gachon University in South Korea.
While encouraging scientific collaboration, CRM’s policy is to maintain strict separation of each institution’s contribution to funding of all projects including clinical trials.
There is potential for exponential growth in the field of regenerative medicine, and despite the initial emphasis on large programmatic development, individual investigators, and small collaborative groups are encouraged to initiate interactions with NIH CRM, although, currently, the Center does not support an extramural grant program.
- Mahendra S. Rao, Francis S. Collins. Steering a New Course for Stem Cell Research: NIH’s Intramural Center for Regenerative Medicine. Stem Cells Translational Medicine. 2012.
- Chiu AY, Rao MS. Cell-based therapy for neural disorders — anticipating challenges. Neurotherapeutics. 2011;8:744-752.
- Rao M, Ahrlund-Richter L, Kaufman DS. Concise review: cord blood banking, transplantation and induced pluripotent stem cell: success and opportunities. Stem Cells. 2012;30:55-60.
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