Center for Human Embryonic Stem Cell Research and Education
Center for Human Embryonic Stem Cell Research and Education
Stem Cell Use:
Embryonic Stem Cell
The goal of this proposal is to establish a premiere center for human embryonic stem cell (hESC) research and education in the state of California. Our center builds on the established excellence of faculty with research organized into four thematic areas: Human embryology, derivation of hESC lines, including disease-specific lines, and SCNT, Cell fate specification and hESC reprogramming,Cancer and cancer stem cells, and Directed differentiation to cardiac and neural lineages. Here, we seek funding to renovate facilities that will house a human embryo/oocyte resource center and database, hESC line derivation, as well as other research and educational training including a central repository for growth, characterization and distribution of hESC lines to scientists in our community. The success of the faculty in this Center in garnering funding for hESC research, including CIRM funding, mandates the expansion of our research facilities. In addition, an accompanying curriculum in Stem Cell Techniques Courses is complementary to the research efforts and builds on a history of teaching excellence. This curriculum will encompass three areas: Basic hESC Biology covering core essentials of hESC biology for individuals with little or no previous experience in hESC research, Advanced or Specialized Stem Cell Techniques courses that will provide individuals with tailored instruction to enhance forward momentum in selected scientific topics, and Systems Biology that reaches across institutions to bring together scientists in hESC and computational research. We anticipate that the outcome of our training initiatives will be both an expansion of knowledge and the building of teams to tackle tough basic and clinical challenges. Finally, we note that our human embryo/oocyte resource center will provide expertise, materials and a complete, decoded database for use of precious resources in hESC research. This will enhance efforts to provide early diagnostics for reproductive and somatic disorders, cancers and onset of disease. Thus, this Center builds on a regionally unique combination of scientific and clinical excellence of Stanford University and neighboring institutions to provide critical research and educational support to scientists in California.
Statement of Benefit to California:
This proposal provides real benefits and value to the citizens of California in that our Center is established with a foundation built on: a scientific faculty that is unsurpassed in knowledge of human development and disease and dedicated to pushing forward in hESC research, a program director with numerous publications on hESCs and extensive experience in the State of California in establishing and directing an hESC Center with both research and teaching components, a Shared Tissue Resource that is supported by the largest, and most accomplished academic IVF (in vitro fertilization) Clinic in California to support research protocols, in an appropriate manner, that range from derivation of normal and affected or disease-specific lines to reprogramming of somatic cells via nuclear transfer, an established, decoded database system that will allow data from hESC research to be translated back to improvements in assessing embryo health (and thus decrease adverse outcomes that impact women’s health such as repetitive miscarriages), a core curriculum that has been successfully implemented for group and individualized instruction, and a central location in Northern California within Silicon Valley that allows us to draw additional expertise from neighboring institutions and open our doors to training diverse members of the scientific community on one contiguous campus. Thus, the combined facility and teaching resource proposed will benefit the citizens of California by consolidating and accelerating research within the northern and central California region as well as by providing advanced training opportunities for investigators and research personnel throughout the State. This will enable a broad range of stem cell applications, promote the rapid translations of new discoveries to the clinic and also provide well characterized clinical grade reagents to support these efforts.
Year 1CIRM support for the core activities and initiatives over the last two years has resulted in the establishment of a robust shared laboratory facility that has allowed us to meet and exceed all of the original goals outlined in our initial proposal including renovation of the laboratory space that accommodates research and educational activities on pluripotent stem cells, reprogramming, cancer stem cells and directed differentiation. The space has been equipped for standard and advanced stem cell applications. In addition, we have established a human tissue bank that incorporates tissues donated for derivation of novel pluripotent stem cell lines and studies of reprogramming and differentiation. Research that has benefit from the shared laboratory space and stem cell courses includes studies of cell senescence and telomerase function in stem cells, human and mouse embryology, derivation of disease-specific human embryonic stem cell lines, urinary incontinence, Marfan syndrome, cancer, cardiovascular health, mitochondrial reprogramming, somatic cell nuclear transfer, diabetes, cystinosis, Parkinson’s disease, autism, and basic studies of growth factor function, somatic and germ line development, establishment of pluripotency and mechanisms underlying reprogramming. In addition to assisting research efforts, our program serves as one of the CIRM-supported centers of education to host students from the CIRM Bridges program enrolled in the California State University system. The Stem Cell Courses have been highly-rated by all participants and have sparked additional course offerings for graduate, medical and postdoctoral students, as well as undergraduates and visiting scholars. Workshops and seminars have been added to cover the latest technologies and provide a venue for interaction of scientists from diverse backgrounds. Overall, the Shared Laboratory and Stem Cell Courses funding has greatly stimulated research on pluripotent stem cells and has had a major effect on the community in direct or indirect support of publications and support of grant applications for additional funding.
Year 2CIRM support for the core activities and initiatives, during the last year, has resulted in the further expansion of our Stanford Center for Human Embryonic Stem Cell Research and Education. This Center has met, and exceeded, all of the original goals outlined in our initial proposal as indicated in the previous report including renovation of laboratory space, active use to support research and education, establishment of the only stem cell bank in the state of California that incorporates stem cell lines (hESCs and iPSCs) as well as donated embryos and oocytes and primary dermal fibroblasts. In addition, we maintain protocols and personnel to obtain skin biopsies and a viral facility to establish lines. Finally, we have expanded to include educational workshops and symposia focused on derivation and differentiation of pluripotent human stem cells and we serve the CIRM Bridges programs of San Jose State University, San Francisco State University and Humboldt State University.
Year 3As described in our previous report (2010), our Center (the shared research laboratory) was established to support research organized into four major categories of interwoven emphasis: 1) Human embryology, derivation of hESCs and SCNT, 2) Cell fate specification and hESC reprogramming, 3) Cancer and cancer stem cells, and 4) Directed differentiation to diverse lineages including the cardiac and neural lineages. CIRM support for the core activities and initiatives, during the last year, has resulted in the further expansion of our Stanford Center for Human Embryonic Stem Cell Research and Education. This Center has met, and exceeded, all of the original goals outlined in our initial proposal and has substantially expanded to further build the only stem cell bank in the state of California that incorporates stem cell lines (hESCs and iPSCs) as well as donated embryos and oocytes and primary dermal fibroblasts,and to incorporate new techniques such as repair of mutations into our research program. The Stem Cells Techniques component of our Center consisted of three activities in 2010-2011, similar to previous years: 1) The Stanford Pluripotent Stem Cell Training Course; 2) Individual Advanced Training; and 3) Seminars and Workshops which include broadly undergraduate educational classes (didactic and laboratory-based). However, we have also expanded our teaching to include derivation of iPSCs with mRNAs and beyond original courses to include undergraduate and graduate quarter-long courses. We continue to also focus on core strengths of embryology, hESCs and courses that remain over-subscribed for personnel at Stanford and in the Bridges programs of San Jose State University, San Francisco State University and Humboldt State University.
Year 4Overall summary of progress from September 1, 2011 to August 31, 2012 is described. CIRM support for the core activities and initiatives, during the last year, has resulted in the further expansion of the Stanford Center for Human Embryonic Stem Cell Research and Education. This Center has met, and exceeded, all of the original goals outlined in our initial proposal and has substantially expanded to further expand the only stem cell bank in the state of California that incorporates stem cell lines (hESCs and iPSCs) as well as donated embryos and oocytes and primary somatic cells. We have incorporated iPSCs throughout the research and educational activities. In addition, we have now incorporated methods of genome editing into our research program. We continue to expand our teaching to include derivation of iPSCs with mRNAs and to reach out beyond original courses to include undergraduate and graduate quarter-long courses. The scope of research taking place in the facility between September 1, 2011, and August 31, 2012 encompassed that described in our previous report, as well as new efforts with an emphasis on: 1) Human embryology and derivation of hESCs, 2) cell fate specification and reprogramming, 3) cancer and cancer stem cells, and 4) directed differentiation to diverse lineages including the hematopoietic, cardiac and neural lineages. Over the last year, more than 25 laboratories received support for their research and in many cases, were able to conduct studies to generate data required to apply for funding for a full research program, thus bringing in funds to California. The Stem Cells Techniques component of our Center consisted of three activities in 2011-2012: 1) The Stanford Pluripotent Stem Cell Training Course; 2) Individual Advanced Training; and 3) Seminars and Workshops which include broadly undergraduate educational classes (didactic and laboratory-based). The outline for our week-long formal training course has been continually improved. We remain overbooked for this course and thus, continue to offer it in the original form but with pertinent updates as needed. We have added iPSCs and reprogramming in lecture form in the last year. We have also designed our first quarter-long immersion in pluripotent stem cells for our incoming graduate students (in Stem Cell Biology and Regenerative Medicine) and have expanded our iPSC reprogramming with mRNA. The Student to Instructor ratio remained no more than 2:1; instructors for the year were knowledgeable on a diverse array of subjects necessary for success from derivation, differentiation and reprogramming to considerations of ethics and privacy of information. Students were again drawn primarily from the San Francisco Bay Area. During this last reporting period, we held 6 courses (expanded from 3-4 annually) on “hESCs and hiPSCs Biology”. The courses cover the basic biology of pluripotent stem cells, culture and differentiation of pluripotent stem cells, methods for the derivation of hiPSCs and derivation of primary culture of MEFs from murine fetal tissues. The course is one week long and consists of lectures, seminars and lab activities. We also provided instruction in an additional course on differentiation of pluripotent stem cells into endothelial cells, cardiomyocytes and smoothe muscle cells (one week of lectures, seminars and lab activities). This course was co-sponsored by the National Institutes of Health, Progenitor Cell Biology Consortium (NHLBI).
- Stem Cells Transl Med (2013) Reprogramming of Fibroblasts From Older Women With Pelvic Floor Disorders Alters Cellular Behavior Associated With Donor Age. (PubMed: 23341439)
- Magn Reson Med (2011) Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma. (PubMed: 22190225)
- PLoS One (2011) SNCA Triplication Parkinson's Patient's iPSC-derived DA Neurons Accumulate alpha-Synuclein and Are Susceptible to Oxidative Stress. (PubMed: 22110584)
- Proc Natl Acad Sci U S A (2011) Skeletogenic phenotype of human Marfan embryonic stem cells faithfully phenocopied by patient-specific induced-pluripotent stem cells. (PubMed: 22178754)
- Hum Mol Genet (2011) Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. (PubMed: 21131292)
- Cell Stem Cell (2011) Donation of embryos for human development and stem cell research. (PubMed: 21474099)
- Magn Reson Med (2011) In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium. (PubMed: 21604295)
- Nature (2011) Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. (PubMed: 21602826)
- Nat Biotechnol (2011) An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. (PubMed: 21841799)
- Cell Stem Cell (2011) LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative Stress. (PubMed: 21362567)
- Toxicol Sci (2010) Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway. (PubMed: 20562217)